· web viewadrenergic dysregulation and pain with and without acute beta-blockade in women with...

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Supplementary Table 1Articles by journal and year

Anesthesiology Anesthesia & Analgesia

British Journal of

AnaesthesiaPAIN

European Journal of

Pain

Journal of Pain Total ACTTION CONSORT

2000 3 3 2 7 1 1 17 - 172001 2 1 2 4 3 0 12 - 122002 2 3 3 5 0 0 13 - 132003 4 4 3 11 0 0 22 - 222006 4 3 4 4 4 2 21 21 -2007 1 2 2 2 2 1 10 10 -2008 3 4 3 6 3 2 21 21 212009 2 7 4 8 4 1 26 26 262010 4 2 2 3 3 0 14 14 142011 2 5 6 6 5 2 26 26 262012 0 6 0 4 3 1 14 14 14Total 27 40 31 60 28 10 196 132 165

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Supplementary Table 2

Coded Articles

Reference Title

Affaitati G et al. Eur J Pain. 2011 Jan;15(1):61-9.

Effects of treatment of peripheral pain generators in fibromyalgia patients.

Agarwal et al. Br J Anaesth. 2008 Oct;101(4):506-10.

Evaluation of intra-operative tramadol for prevention of catheter-related bladder discomfort: a prospective, randomized, double-blind study.

Aguirre et al. Anesth Analg. 2012 Feb;114(2):456-61.

Continuous epicapsular ropivacaine 0.3% infusion after minimally invasive hip arthroplasty: a prospective, randomized, double-blinded, placebo-controlled study comparing continuous wound infusion with morphine patient-controlled analgesia.

Aida et al. Pain 84 (2000) 169-173Involvement of presurgical pain in preemptive analgesia for orthopedic surgery: a randomized double blind study

Aissaoui et al. Anesth Analg. 2008 Aug;107(2):625-9.

A randomized controlled trial of pudendal nerve block for pain relief after episiotomy.

Angst et al. / Pain 106 (2003) 49–57Short-term infusion of the μ-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal

Angst et al. 2012 Pain 153(7):1397-409Pain sensitivity and opioid analgesia: a pharmacogenomic twin study.

Angst et al. Anesthesiology. 2000 Feb;92(2):312-24.

Lumbar epidural morphine in humans and supraspinal analgesia to experimental heat pain.

Angst MS et al. Pain. 2009 Mar;142(1-2):17-26.

No evidence for the development of acute tolerance to analgesic, respiratory depressant and sedative opioid effects in humans.

Arendt-Nielsen et al. Anesthesiology. 2009 Sep;111(3):616-24.

Analgesic efficacy of peripheral kappa-opioid receptor agonist CR665 compared to oxycodone in a multi-modal, multi-tissue experimental human pain model: selective effect on visceral pain.

Arendt-Nielsen L et al. Eur J Pain. 2008 Jul;12(5):661-70.

Interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans.

Atanassoff et al. Anesthesiology. 2001 Sep.95(3):627-31.

Ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in outpatient surgery.

Athanasos et al. 2006 Pain 120(3):267-75

Methadone maintenance patients are cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations.

Aveline C et al. Eur J Pain. 2009 Jul;13(6):613-9.

Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam.

Aveline et al. 2006 Eur J Pain. 10(7):653-8.Peroperative ketamine and morphine for postoperative pain control after lumbar disk surgery.

Ayesh EE et al. Pain. 2008 Jul Effects of intra-articular ketamine on pain and

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15;137(2):286-94somatosensory function in temporomandibular joint arthralgia patients.

Baad-Hansen et al. 2007 Pain. 2007 May;129(1-2):46-54.

Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain.

Baba et al. 2012 Eur J Pain 16(8):1137-47Effects of dexmedetomidine on conditioned pain modulation in humans.

Bandschapp et al. Anesthesiology. 2010 Aug;113(2):421-8.

Analgesic and antihyperalgesic properties of propofol in a human pain model.

Bandschapp O et al. Pain. 2011 Jun;152(6):1304-10.

Tropisetron blocks analgesic action of acetaminophen: a human pain model study.

Belavy et al. Br J Anaesth. 2009 Nov;103(5):726-30.

Ultrasound-guided transversus abdominis plane block for analgesia after Caesarean delivery.

Bharti et al. Anesth Analg. 2011 Jun;112(6):1504-8.

The efficacy of a novel approach to transversus abdominis plane block for postoperative analgesia after colorectal surgery.

Bijur et al. 2006 J Pain. 7(2):75-81.

Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance analgesia in emergency department patients.

Binning AR et al. Eur J Pain. 2011 Apr;15(4):402-8.

A randomised controlled trial on the efficacy and side-effect profile (nausea/vomiting/sedation) of morphine-6-glucuronide versus morphine for post-operative pain relief after major abdominal surgery.

Bischoff et al. Anesth Analg. 2012 Jun;114(6):1323-9.

Ultrasound-guided ilioinguinal/iliohypogastric nerve blocks for persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial.

Bondok & Abd El-Hady. Br J Anaesth. 2006 Sep;97(3):389-92.

Intra-articular magnesium is effective for postoperative analgesia in arthroscopic knee surgery.

Boselli et al. Anesth Analg. 2003 Apr;96(4):1173-7.

Ropivacaine 0.15% plus sufentanil 0.5 microg/mL and ropivacaine 0.10% plus sufentanil 0.5 microg/mL are equivalent for patient-controlled epidural analgesia during labor.

Brown et al. 2012 J Pain. 13(8):790-8. Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial.

Bucciero et al. Anesth Analg. 2011 Nov;113(5):1266-71.

Intraperitoneal ropivacaine nebulization for pain management after laparoscopic cholecystectomy: a comparison with intraperitoneal instillation.

Candido et al. Anesthesiology. 2010 Dec;113(6):1419-26.

Buprenorphine enhances and prolongs the postoperative analgesic effect of bupivacaine in patients receiving infragluteal sciatic nerve block.

Cepeda et al. / Pain 96 (2002) 73–79

The combination of low dose of naloxone and morphine in PCA does not decrease opioid requirements in the postoperative period

Chen DW et al. Eur J Pain. 2010 May;14(5):529-34.

Continuous intra-articular infusion of bupivacaine for post-operative pain relief after total hip arthroplasty: a

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randomized, placebo-controlled, double-blind study.

Cheong et al. Anesth Analg. 2002 Nov;95(5):1293-6. Ephedrine reduces the pain from propofol injection.

Choi W et al. Pain 2011 Mar;152(3):481-7

Radiofrequency treatment relieves chronic knee osteoarthritis pain: a double-blind randomized controlled trial.

Chu et al. 2012 Pain 153(5):974-81Modulation of remifentanil-induced postinfusion hyperalgesia by the β-blocker propranolol in humans.

Chu LF et al. J Pain. 2011 Jan;12(1):108-15.

The endogenous opioid system is not involved in modulation of opioid-induced hyperalgesia.

Clément et al. Br J Anaesth. 2002 Jun;88(6):809-13.

Epidural analgesia with 0.15% ropivacaine plus sufentanil 0.5 microgram ml-1 versus 0.10% bupivacaine plus sufentanil 0.5 microgram ml-1: a double-blind comparison during labour.

Cole et al. Br J Anaesth. 2000 Aug;85(2):233-7.

Efficacy and respiratory effects of low-dose spinal morphine for postoperative analgesia following knee arthroplasty.

Cuatrecasas et al. 2012 Pain. 153(7):1382-9.

Growth hormone treatment for sustained pain reduction and improvement in quality of life in severe fibromyalgia

Dahaba AA et al. Eur J Pain. 2009 Sep;13(8):861-4

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery.

Dahl et al. Anesth Analg. 2000 Jun;90(6):1419-22.

Does ketamine have preemptive effects in women undergoing abdominal hysterectomy procedures?

Danou et al. Anesth Analg. 2000 Mar;90(3):672-6.

The analgesic efficacy of intravenous tenoxicam as an adjunct to patient-controlled analgesia in total abdominal hysterectomy.

De Kock et al. / Pain 92 (2001) 373±380‘Balanced analgesia’ in the perioperative period: is there a place for ketamine?

De Oliveira et al. Anesth Analg. 2011 Nov;113(5):1218-25.

A dose-ranging study of the effect of transversus abdominis block on postoperative quality of recovery and analgesia after outpatient laparoscopy.

De Oliveira et al. Anesth Analg. 2012 Aug;115(2):262-7.

Systemic lidocaine to improve postoperative quality of recovery after ambulatory laparoscopic surgery.

De Oliveira et al. Br J Anaesth. 2011 Sep;107(3):362-71.

Dose ranging study on the effect of preoperative dexamethasone on postoperative quality of recovery and opioid consumption after ambulatory gynaecological surgery.

Du Manoir et al. Br J Anaesth. 2003 Dec;91(6):836-41.

Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery.

Dualé C et al. Eur J Pain. 2009 May;13(5):497-505.

Perioperative ketamine does not prevent chronic pain after thoracotomy.

Eisenach, Carpenter et al. / Pain 101 (2003) 89–95

Analgesia from a peripherally active κ-opioid receptor agonist in patients with chronic pancreatitis

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Eisenach, Rauck et al. / Pain 105 (2003) 65–70

Intrathecal, but not intravenous adenosine reduces allodynia in patients with neuropathic pai

Elkind et al. 2006 J Pain. 2006 Oct;7(10):688-96.

A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis.

Elsharnouby et al. Anesth Analg. 2008 May;106(5):1548-52.

Intraarticular injection of magnesium sulphate and/or bupivacaine for postoperative analgesia after arthroscopic knee surgery.

Ernberg et al. / Pain 101 (2003) 275–282Effects on muscle pain by intramuscular injection of granisetron in patients with fibromyalgia

Ernberg et al. / Pain 84 (2000) 339±346

Effect of propranolol and granisetron on experimentally induced pain and allodynia/hyperalgesia by intramuscular injection of serotonin into the human masseter muscle

Ernberg M et al. Pain. 2011 Sep;152(9):1988-96.

Efficacy of botulinum toxin type A for treatment of persistent myofascial TMD pain: a randomized, controlled, double-blind multicenter study.

Essving et al. Anesth Analg. 2011 Oct;113(4):926-33.

Local infiltration analgesia versus intrathecal morphine for postoperative pain management after total knee arthroplasty: a randomized controlled trial.

Eti et al. Anesth Analg. 2006 Apr;102(4):1174-6.

Does bilateral superficial cervical plexus block decrease analgesic requirement after thyroid surgery?

Fant et al. Br J Anaesth. 2011 Nov;107(5):782-9.

Thoracic epidural analgesia or patient-controlled local analgesia for radical retropubic prostatectomy: a randomized, double-blind study.

Filitz J et al. Pain. 2008;136:262–270Supra-additive effects of tramadol and acetaminophen in a human pain model

Finlayson HC et al. Pain. 2011 Sep;152(9):2023-8.

Botulinum toxin injection for management of thoracic outlet syndrome: a double-blind, randomized, controlled trial.

Fischer et al. Anesthesiology. 2000 Jun;92(6):1588-93.

Ropivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison.

Fournier et al. Anesth Analg. 2000 Apr;90(4):918-22.

A comparison of intrathecal analgesia with fentanyl or sufentanil after total hip replacement.

Fournier et al. Br J Anaesth. 2002 Oct;89(4):562-6.

Epinephrine and clonidine do not improve intrathecal sufentanil analgesia after total hip replacement.

Fukunaga et al. / Pain 101 (2003) 129–138

Characterization of the analgesic actions of adenosine: comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures

Gan et al. Anesth Analg. 2012 Nov;115(5):1212-20.

A novel injectable formulation of diclofenac compared with intravenous ketorolac or placebo for acute moderate-to-severe pain after abdominal or pelvic surgery: a multicenter, double-blind, randomized, multiple-dose study.

Gazerani et al. 2006 Pain. 2006 Jun;122(3):315-25.

The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental

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human model of trigeminal sensitization.

Gazerani P et al. Pain. 2009 Jan;141(1-2):60-9.

Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin.

Gear et al. The Journal of Pain, (2000) 1:122-127

Action of naloxone on gender-dependent analgesic and antianalgesic effects of nalbuphine in humans

Gehling et al. Br J Anaesth. 2010 Jun;104(6):761-7.

Postoperative analgesia with parecoxib, acetaminophen, and the combination of both: a randomized, double-blind, placebo-controlled trial in patients undergoing thyroid surgery.

Göbel et al. 2006 Pain. 125(1-2):82-8.

Efficacy and safety of a single botulinum type A toxin complex treatment (Dysport) for the relief of upper back myofascial pain syndrome: results from a randomized double-blind placebo-controlled multicentre study.

Goebel A et al. Eur J Pain. 2008 Apr;12(3):266-74.

Buprenorphine injection to the stellate ganglion in the treatment of upper body chronic pain syndromes.

Goodman et al. Anesth Analg. 2009 Jan;108(1):246-51.

A randomized trial of breakthrough pain during combined spinal-epidural versus epidural labor analgesia in parous women.

Gormsen et al. Anesth Analg. 2009 Apr;108(4):1311-9.

The efficacy of the AMPA receptor antagonist NS1209 and lidocaine in nerve injury pain: a randomized, double-blind, placebo-controlled, three-way crossover study.

Gottrup et al. Anesthesiology. 2006 Mar;104(3):527-36.

Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain.

Gottrup et al. Br J Anaesth. 2000 Feb;84(2):155-62.

Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.

Grady et al. Anesth Analg. 2012 Nov;115(5):1078-84.

The effect of perioperative intravenous lidocaine and ketamine on recovery after abdominal hysterectomy.

Graven-Nielsen et al. / Pain 85 (2000) 483±491

Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients

Grémeau-Richard C et al. Pain. 2010 Apr;149(1):27-32.

Effect of lingual nerve block on burning mouth syndrome (stomatodynia): a randomized crossover trial.

Griffiths et al. Anesth Analg. 2010 Sep;111(3):797-801.

Transversus abdominis plane block does not provide additional benefit to multimodal analgesia in gynecological cancer surgery.

Habib et al. Anesthesiology. 2008 Dec;109(6):1085-91.

Phase 2, double-blind, placebo-controlled, dose-response trial of intravenous adenosine for perioperative analgesia.

Hauck et al. 2006 Eur J Pain. 10(8):757-65. Clonidine effects on pain evoked SII activity in humans.

Hay JL et al. Eur J Pain. 2011 Mar;15(3):293-8

Potentiation of buprenorphine antinociception with ultra-low dose naltrexone in healthy subjects.

Hill et al. Anesthesiology. 2006 May;104(5):1047-53.

Efficacy of single-dose, multilevel paravertebral nerve blockade for analgesia after thoracoscopic procedures.

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Holte et al. Anesthesiology. 2002 Jun;96(6):1331-5.

Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers.

Holthusen et al. / Pain 88 (2000) 295±302

Effect of pre- or post-traumatically applied i.v. lidocaine on primary and secondary hyperalgesia after experimental heat trauma in humans

Hubbarb et al. Br J Anaesth. 2003 Feb;90(2):166-72.

Parecoxib sodium has opioid-sparing effects in patients undergoing total knee arthroplasty under spinal anaesthesia.

Hügler P et al. Eur J Pain. 2002;6(6):435-45.

Prevention of postherpetic neuralgia with varicella-zoster hyperimmune globulin.

Hwang et al. Br J Anaesth. 2010 Jan;104(1):89-93.

I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia.

Ilfeld BM et al. Pain. 2010 Sep;150(3):477-84.

A multicenter, randomized, triple-masked, placebo-controlled trial of the effect of ambulatory continuous femoral nerve blocks on discharge-readiness following total knee arthroplasty in patients on general orthopaedic wards.

Ilfeld et al. Anesth Analg. 2003 Sep;97(3):706-12.

Continuous infraclavicular perineural infusion with clonidine and ropivacaine compared with ropivacaine alone: a randomized, double-blinded, controlled study.

Ilfeld et al. Anesthesiology. 2008 Sep;109(3):491-501.

Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty: a dual-center, randomized, triple-masked, placebo-controlled trial.

Jeffs et al. Br J Anaesth. 2002 Sep;89(3):424-7.

Comparison of morphine alone with morphine plus clonidine for postoperative patient-controlled analgesia.

Jokela et al. Anesth Analg. 2009 Aug;109(2):607-15.

The effective analgesic dose of dexamethasone after laparoscopic hysterectomy.

Jones et al. Br J Anaesth. 2009 Jan;102(1):76-9. Parecoxib for analgesia after craniotomy.

Jørgensen et al. Br J Anaesth. 2001 Nov;87(5):727-32.

Effect of epidural bupivacaine vs combined epidural bupivacaine and morphine on gastrointestinal function and pain after major gynaecological surgery.

Jørum et al. / Pain 101 (2003) 229–235

Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-d-aspartate (NMDA) receptor antagonist ketamine – a double-blind, cross-over comparison with alfentanil and placebo

Ju H et al. Eur J Pain. 2008 Apr;12(3):378-84.

Comparison of epidural analgesia and intercostal nerve cryoanalgesia for post-thoracotomy pain control.

Juhl et al. 2006 Eur J Pain. 2006 May;10(4):371-7.

Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.

Kaba et al. Anesthesiology. 2007 Jan;106(1):11-8.

Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy.

Karanikolas et al. Anesthesiology. 2011 May;114(5):1144-54.

Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: a

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prospective, randomized, clinical trial.

Katz et al. Anesthesiology. 2003 Jun;98(6):1449-60.

Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization.

Katz N et al. Pain. 2011 Oct;152(10):2248-58.

Efficacy and safety of tanezumab in the treatment of chronic low back pain.

Kawamata et al. / Pain 100 (2002) 77–89Experimental incision-induced pain in human skin: effects of systemic lidocaine on flare formation and hyperalgesia

Kern D et al. Pain. 2008 Apr;135(3):291-9Pharmacological dissection of the paradoxical pain induced by a thermal grill.

Kern D et al. Pain. 2008 Oct 31;139(3):653-9.

Effects of morphine on the experimental illusion of pain produced by a thermal grill.

Kindler LL, et al. J Pain. 2011 Mar;12(3):340-51

Drug response profiles to experimental pain are opioid and pain modality specific.

Koppert et al. / Pain 106 (2003) 91–99Naloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humans

Koppert et al. / Pain 85 (2000) 217±224Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action

Koppert et al. Anesthesiology, 2003 Jul;99(1):152-9.

Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans.

Koppert et al. Anesthesiology. 2001 Aug:95(2):395-402.

A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine.

Kuivalainen AM et al. Eur J Pain. 2010 Feb;14(2):160-3.

Comparison of articaine and lidocaine for infiltration anaesthesia in patients undergoing bone marrow aspiration and biopsy.

Kumar et al. Anesth Analg. 2006 Sep;103(3):696-702.

The effect of intravenous ketorolac on capsaicin-induced deep tissue hyperalgesia.

Kvarstein G et al. Pain. 2009 Oct;145(3):279-86.

A randomized double-blind controlled trial of intra-annular radiofrequency thermal disc therapy--a 12-month follow-up.

Landau R et al. Pain. 2008 Sep 30;139(1):5-14.

Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women.

Lemming et al. 2007 Eur J Pain. 11(7):719-32.

Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine).

Lena et al. Br J Anaesth. 2003 Mar;90(3):300-3.

Intrathecal morphine and clonidine for coronary artery bypass grafting.

Lenz et al. Anesth Analg. 2009 Oct;109(4):1279-83.

A comparison of intravenous oxycodone and intravenous morphine in patient-controlled postoperative analgesia after laparoscopic hysterectomy.

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Leung et al. / Pain 91 (2001) 177±187

Concentration–effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain

Light KC et al. J Pain. 2009 May;10(5):542-52.

Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder.

Lin et al. Br J Anaesth. 2009 Jan;102(1):117-22.

Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia.

Lipszyc et al. Br J Anaesth. 2011 May;106(5):724-31.

Remifentanil patient-controlled analgesia effect-site target-controlled infusion compared with morphine patient-controlled analgesia for treatment of acute pain after uterine artery embolization.

List et al. / Pain 94 (2001) 275–282Intra-articular morphine as analgesic in temporomandibular joint arthralgia/osteoarthritis

List et al. 2006 Pain. 2006 Jun;122(3):306-14.

Effect of local anesthesia on atypical odontalgia--a randomized controlled trial.

Loftus et al. Anesthesiology. 2010 Sep;113(3):639-46.

Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery.

Lotsch, M.S. Angst / Pain 102 (2003) 151–161

The μ-opioid agonist remifentanil attenuates hyperalgesia evoked by blunt and punctuated stimuli with different potency: a pharmacological evaluation of the freeze lesion in humans

Lunn et al. Br J Anaesth. 2011 Feb;106(2):230-8.

Effect of high-dose preoperative methylprednisolone on pain and recovery after total knee arthroplasty: a randomized, placebo-controlled trial.

Lynch et al. / Pain 103 (2003) 111–117

Intravenous adenosine alleviates neuropathic pain: a double blind placebo controlled crossover trial using an enriched enrolment design

Macarthur et al. Anesth Analg. 2010 Jan;110(1):159-64.

A randomized, double-blind, placebo-controlled trial of epidural morphine analgesia after vaginal delivery.

Marinangeli et al. Eur J Pain (2002) 6: 35±42

Clonidine for treatment of postoperative pain: a dose-finding study

Martin et al. Anesthesiology. 2008 Jul;109(1):118-23.

Lack of impact of intravenous lidocaine on analgesia, functional recovery, and nociceptive pain threshold after total hip arthroplasty.

McKay et al. Anesth Analg. 2009 Dec;109(6):1805-8.

Systemic lidocaine decreased the perioperative opioid analgesic requirements but failed to reduce discharge time after ambulatory surgery.

McMorrow et al. Br J Anaesth. 2011 May;106(5):706-12.

Comparison of transversus abdominis plane block vs spinal morphine for pain relief after Caesarean section.

Mendola et al. Br J Anaesth. 2009 Mar;102(3):418-23.

Thoracic epidural analgesia in post-thoracotomy patients: comparison of three different concentrations of levobupivacaine and sufentanil.

Michelet et al. Br J Anaesth. 2007 Adding ketamine to morphine for patient-controlled

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Sep;99(3):396-403.

analgesia after thoracic surgery: influence on morphine consumption, respiratory function, and nocturnal desaturation.

Mikkelsen et al. Br J Anaesth. 2001 Jun;86(6):871-3.

Effect of intravenous magnesium on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers.

Mitchell, M.T. Fallon / Pain 97 (2002) 275–281

A single infusion of intravenous ketamine improves pain relief in patients with critical limb ischaemia: results of a double blind randomised controlled trial

Moller et al. Anesth Analg. 2007 Dec;105(6):1848-51.

Thoracic paravertebral block for breast cancer surgery: a randomized double-blind study.

Munts AG et al. Eur J Pain. 2010 May;14(5):523-8.

Efficacy and safety of a single intrathecal methylprednisolone bolus in chronic complex regional pain syndrome.

Munts AG et al. Pain. 2009 Nov;146(1-2):199-204

Intrathecal glycine for pain and dystonia in complex regional pain syndrome.

Murdoch et al. Anesth Analg. 2002 Feb;94(2):438-44.

The efficacy and safety of three concentrations of levobupivacaine administered as a continuous epidural infusion in patients undergoing orthopedic surgery.

Murphy GS et al. Anesthesiology. 2011 Apr;114(4):882-90.

Preoperative dexamethasone enhances quality of recovery after laparoscopic cholecystectomy: effect on in-hospital and postdischarge recovery outcomes.

Neziri et al. 2012 Pain. 153(2):311-8.Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients.

Ngan Kee et al. Anesthesiology. 2010 Aug;113(2):445-53.

Determination and comparison of graded dose-response curves for epidural bupivacaine and ropivacaine for analgesia in laboring nulliparous women.

Niruthisard et al. Anesth Analg. 2007 Sep;105(3):822-824.

Improving the analgesic efficacy of intrathecal morphine with parecoxib after total abdominal hysterectomy.

Nixdorf et al. / Pain 99 (2002) 465–473Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain

Noppers I et al. Eur J Pain. 2011 Oct;15(9):942-9.

Absence of long-term analgesic effect from a short-term S-ketamine infusion on fibromyalgia pain: a randomized, prospective, double blind, active placebo-controlled trial.

Ortner et al. 2012 Eur J Pain 16(4):562-73Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia.

Peng B et al. Pain. 2010 Apr;149(1):124-9.

A randomized placebo-controlled trial of intradiscal methylene blue injection for the treatment of chronic discogenic low back pain.

Perez RS et al. J Pain. 2008 Aug;9(8):678-86.

Treatment of patients with complex regional pain syndrome type I with mannitol: a prospective, randomized, placebo-controlled, double-blinded study.

Petersen et al. Anesth Analg. 2012 Sep;115(3):527-33.

The beneficial effect of transversus abdominis plane block after laparoscopic cholecystectomy in day-case surgery: a randomized clinical trial.

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Porta / Pain 85 (2000) 101±105

A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm

Rashiq et al. / Pain 106 (2003) 119–125The effect of opioid analgesia on exercise test performance in chronic low back pain

Rathmell et al. Anesth Analg. 2003 Nov;97(5):1452-7.

Intrathecal morphine for postoperative analgesia: a randomized, controlled, dose-ranging study after hip and knee arthroplasty.

Ribeiro-Dasilva MC et al. Pain 2011 Mar;152(3):614-22

Evaluation of menstrual cycle effects on morphine and pentazocine analgesia

Riest et al. Br J Anaesth. 2008 Feb;100(2):256-62.

Preventive effects of perioperative parecoxib on post-discectomy pain.

Rosseland et al. / Pain 104 (2003) 25–34

Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain, demonstrates large variation in need of analgesics, and finds no analgesic effect of IA ketamine compared with IA saline

Roussier et al. Br J Anaesth. 2006 Apr;96(4):492-6.

Patient-controlled cervical epidural fentanyl compared with patient-controlled i.v. fentanyl for pain after pharyngolaryngeal surgery.

Rugyte et al. 2007 Eur J Pain. 211(6):694-9.

Intravenous ketoprofen as an adjunct to patient-controlled analgesia morphine in adolescents with thoracic surgery: a placebo controlled double-blinded study.

Schenk et al. Anesth Analg. 2006 Nov;103(5):1311-7.

Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia.

Schulte et al. 2006 Eur J Pain. 10(8):733-41Reduction of human experimental muscle pain by alfentanil and morphine.

Schwartzman RJ et al. Pain. 2009 Dec 15;147(1-3):107-15.

Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study.

Sen H et al. Anesth Analg. 2009 Oct;109(4):1327-30.

The analgesic effect of paracetamol when added to lidocaine for intravenous regional anesthesia.

Sen S et al. Br J Anaesth. 2006 Sep;97(3):408-13.

The analgesic effect of lornoxicam when added to lidocaine for intravenous regional anaesthesia.

Sigtermans MJ et al. Pain. 2009 Oct;145(3):304-11

Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1.

Simmonds et al. Anesth Analg. 2009 Dec;109(6):1972-80.

The effect of single-dose propofol injection on pain and quality of life in chronic daily headache: a randomized, double-blind, controlled trial.

Sjölund et al. European Journal of Pain (2001) 5: 199–207

Systemic adenosine infusion reduces the area of tactile allodynia in neuropathic pain following peripheral nerve injury: a multi-centre, placebo-controlled study

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Smet et al. Br J Anaesth. 2008 Jan;100(1):99-103.

Randomized controlled trial of patient-controlled epidural analgesia after orthopaedic surgery with sufentanil and ropivacaine 0.165% or levobupivacaine 0.125%.

Smith TW et al. Eur J Pain. 2009 Mar;13(3):293-9.

Efficacy and safety of morphine-6-glucuronide (M6G) for postoperative pain relief: a randomized, double-blind study.

Sneyd et al. Br J Anaesth. 2007 May;98(5):672-6.

Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction.

Song JW et al. Anesth Analg. 2011 Aug;113(2):390-7.

Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy.

Staud R et al. Pain. 2009 Sep;145(1-2):96-104

Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: a randomized, double-blind, placebo-controlled study.

Steinlechner et al. Br J Anaesth. 2006 Apr;96(4):444-9.

Magnesium moderately decreases remifentanil dosage required for pain management after cardiac surgery.

Stevens R et al. Anesthesiology. 2000 Jul;93(1):115-21.

Lumbar plexus block reduces pain and blood loss associated with total hip arthroplasty.

Suzuki et al. Anesthesiology. 2006 Jul;105(1):111-9.

Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy.

Taboada et al. Anesthesiology. 2009 Jan;110(1):150-4.

Comparison of continuous infusion versus automated bolus for postoperative patient-controlled analgesia with popliteal sciatic nerve catheters.

Tan N et al. Anesth Analg. 2002 Jan;94(1):199-202.

Suprascapular nerve block for ipsilateral shoulder pain after thoracotomy with thoracic epidural analgesia:a double-blind comparison of 0.5% bupivacaine and 0.9% saline.

Tramer, C.J. Glynn / Pain 99 (2002) 235–241

Magnesium bier's block for treatment of chronic limb pain: a randomised, double-blind, cross-over study

Tröster et al. Anesthesiology. 2006 Nov;105(5):1016-23.

Modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by parecoxib in humans.

Tugnoli et al. 2007 Pain. 130(1-2):76-83. Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin.

Vallejo et al. 2007 J Pain 8(12):970-5

Epidural labor analgesia: continuous infusion versus patient-controlled epidural analgesia with background infusion versus without a background infusion

Velasco F et al. Pain. 2009 Dec 15;147(1-3):91-8.

Motor cortex electrical stimulation applied to patients with complex regional pain syndrome.

Vergne-Salle P et al. Eur J Pain. 2011 May;15(5):509-14.

A randomised, double-blind, placebo-controlled trial of dolasetron, a 5-hydroxytryptamine 3 receptor antagonist, in patients with fibromyalgia.

Vergnion et al. Anesth Analg. 2001 Jun;92(6):1543-6.

Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation.

Wang H et al. J Pain. 2008 Dec;9(12):1088-95.

Effect of morphine and pregabalin compared with diphenhydramine hydrochloride and placebo on hyperalgesia and allodynia induced by intradermal

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capsaicin in healthy male subjects.

Warncke et al. / Pain 86 (2000) 293±303

Preinjury treatment with morphine or ketamine inhibits the development of experimentally induced secondary hyperalgesia in man

Wheeler et al. / Pain 94 (2001) 255–260 Botulinum toxin A for the treatment of chronic neck pain

White et al. Anesth Analg. 2003 Nov;97(5):1303-9.

The use of a continuous popliteal sciatic nerve block after surgery involving the foot and ankle: does it improve the quality of recovery?

White et al. Anesthesiology. 2003 Oct;99(4):918-23.

Use of a continuous local anesthetic infusion for pain management after median sternotomy.

Williams DL et al. Br J Anaesth. 2011 Sep;107(3):398-403. Effect of intravenous parecoxib on post-craniotomy pain.

Wilson JA et al. Pain. 2008 Mar;135(1-2):108-18

A randomised double blind trial of the effect of pre-emptive epidural ketamine on persistent pain after lower limb amputation.

Woehick et al. Anesthesiology. 2003 Oct;9(4):924-8.

Acetazolamide reduces referred postoperative pain after laparoscopic surgery with carbon dioxide insufflation.

Wolter et al. 2012 Eur J Pain. 16(5):648-55

Effects of sub-perception threshold spinal cord stimulation in neuropathic pain: a randomized controlled double-blind crossover study.

Wu et al. Anesthesiology. 2002 Apr;96(4):841-8.

Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial.

Zachrisson et al. European Journal of Pain (2002) 6: 455–466

Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome—a randomised controlled trial

Zakine et al. Anesth Analg. 2008 Jun;106(6):1856-61.

Postoperative ketamine administration decreases morphine consumption in major abdominal surgery: a prospective, randomized, double-blind, controlled study.

Zeidan et al. Anesth Analg. 2008 Jul;107(1):292-9.

Intraarticular tramadol-bupivacaine combination prolongs the duration of postoperative analgesia after outpatient arthroscopic knee surgery.

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Supplementary Table 3Reporting AE methodology

Pain type in non-IV trials Journal type Sponsor

All trials (n=132)

Chronic (n=17)

Acute (n=33)

Anes. journals (n=66)

Pain journals(n=66)

Industry (n=30)

Other (n=102)

Report AE assessment methods P=0.053 P=0.071 P=0.129Yes (reported specific methods) 106 (80.3%) 12 (71%) 25 (76%) 55 (83.3%) 51 (77.3%) 27 (90.0%) 79 (77.5%)

No (AEs collected, method not specified) 15 (11.4%) 1 (6%) 7 (21%) 9 (13.6%) 6 (9.1%) 3 (10.0%) 12 (11.8%)

No AE information reported 11 (8.3%) 4 (24%) 1 (3%) 2 (3.0%) 9 (13.6%) 0 (0.0%) 11 (10.8%)

AE assessment methods (trials can use more than 1 method)

Pt spontaneous report or responses to open ended questioning

28 (21.2%) 10 (59%) 3 (9%) 10 (15.2%) 18 (27.3%) 11 (36.7%) 17 (16.7%)

Pt responses to specific AE prompts or a scale of drug associated AEs

80 (60.6%) 1 (6%) 15 (45%) 52 (78.8%) 28 (42.4%) 14 (46.7%) 66 (64.7%)

Physical exam 29 (22.0%) 5 (29%) 6 (18%) 9 (13.6%) 20 (30.3%) 10 (33.3%) 19 (18.6%)Vital signs, lab procedures, diagnostic tests, radiological exam

89 (67.4%) 4 (24%) 17 (52%) 43 (65.2%) 46 (69.7%) 28 (93.3%) 61 (59.8%)

Not specified 15 (11.4%) 1 (6%) 7 (21%) 9 (13.6%) 6 (9.1%) 3 (10.0%) 12 (11.8%)

Specify timing of AE data collection 95 (72.0%) 8 (47%) 26 (79%) 56 (84.8%) 39 (59.1%) 20 (66.7%) 75 (73.5%)

Code AE dataCOSTART 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)MedDRA 1 (0.8%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)Another standardized system 1 (0.8%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)Researcher defined terms 5 (3.8%) 1 (6%) 0 (0.0%) 1 (1.5%) 4 (6.1%) 0 (0.0%) 5 (4.9%)No/not specified 114 (86.4%) 12 (71%) 32 (97%) 63 (95.5%) 51 (77.3%) 29 (96.7%) 85 (83.3%)No AE information reported 11 (8.3%) 4 (24%) 1 (3%) 2 (3.0%) 9 (13.6%) 0 (0.0%) 11 (10.8%)

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Describe scale used to rate AE severity 42 (31.8%) 1 (6%) 13 (39%) 26 (39.4%) 16 (24.2%) 10 (33.3%) 32 (31.4%)

AE severity definitions provided 34 (25.8%) 3 (18%) 10 (30%) 20 (30.3%) 14 (21.2%) 9 (30.0%) 25 (24.5%)

Statistical plans presented for AE data P=0.008 P=0.068 P=0.052

Descriptive statistics to be presented 3 (2.3%) 0 (0.0%) 0 (0.0%) 1 (1.5%) 2 (3.0%) 2 (6.7%) 1 (1.0%)

Statistical comparisons between arms to be presented 30 (22.7%) 0 (0.0%) 9 (27%) 18 (27.3%) 12 (18.2%) 5 (16.7%) 25 (24.5%)

Other 2 (1.5%) 0 (0.0%) 0 (0.0%) 2 (3.0%) 0 (0.0%) 1 (3.3%) 1 (1.0%)No statistical plans presented 86 (65.2%) 13 (76%) 23 (70%) 43 (65.2%) 43 (65.2%) 22 (73.3%) 64 (62.7%)No AE information reported 11 (8.3%) 4 (24%) 1 (3%) 2 (3.0%) 9 (13.6%) 0 (0.0%) 11 (10.8%)

IV = Intravenous; Anes. = Anesthesiology; COSTART = Coding Symbols for a Thesaurus of Adverse Reaction Terms (http://www.nlm.nih.gov/research/umls/sourcereleasedocs/current/CST/); MedDRA = Medical Dictionary for Regulatory Activities (http://www.meddra.org)

http://www.meddra.org/

http://www.nlm.nih.gov/research/umls/sourcereleasedocs/current/CST/

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Supplementary Table 4Reporting all participant withdrawal


All trials (n=132)

Chronic (n=17)

Acute (n=33)


Pain journals(n=66)

Industry (n=30)

Other (n=102)

Report withdrawals P=0.461 P=0.292 P=0.124Separately for each arm 64 (48.5%) 9 (53%) 18 (54%) 37 (56.1%) 27 (40.9%) 14 (46.7%) 50 (49.0%)Separately for a selection of arms 1 (0.8%) 0 (0%) 0 (0%) 1 (1.5%) 0 (0.0%) 1 (3.3%) 0 (0.0%)

Globally for all arms 19 (14.4%) 1 (6%) 5 (15%) 7 (10.6%) 12 (18.2%) 3 (10%) 16 (15.7%)No withdrawals occurred 29 (22.0%) 5 (29%) 4 (12%) 12 (18.2%) 17 (25.8%) 10 (33.3%) 19 (18.6%)Withdrawals not reported 19 (14.4%) 2 (12%) 6 (18%) 9 (13.6%) 10 (15.2%) 2 (6.7%) 17 (16.7%)

Report reasons for withdrawals P=0.502 P=0.772 P=0.241Yes 82 (62.1%) 10 (59%) 22 (67%) 44 (66.7%) 38 (57.5%) 18 (60.0%) 64 (62.7%)No, reasons for withdrawal not specified/reported 2 (1.5%) 0 (0%) 1 (3%) 1 (1.5%) 1 (1.5%) 0 (0.0%) 2 (2.0%)

No withdrawals occurred 29 (22.0%) 5 (29%) 4 (12%) 12 (18.2%) 17 (25.8%) 10 (33.3%) 19 (18.6%)Withdrawals not reported 19 (14.4%) 2 (12%) 6 (18%) 9 (13.6%) 10 (15.2%) 2 (6.7%) 17 (16.7%)

Was it clear who initiated study withdrawal (i.e., participant or study staff)

Yes, for all withdrawals 74 (56.1%) 10 (59%) 20 (61%) 38 (57.6%) 36 (54.5%) 17 (56.7%) 57 (55.9%)Yes, for some withdrawals 4 (3.0%) 0 (0%) 2 (6%) 2 (3.0%) 2 (3.0%) 1 (3.3%) 3 (2.9%)No 4 (3.0%) 0 (0%) 0 (0%) 4 (6.1%) 0 (0.0%) 0 (0.0%) 4 (3.9%)Not applicable 50 (37.9%) 7 (41%) 11 (33%) 22 (33.3%) 28 (42.4%) 12 (40.0%) 38 (37.3%)

Withdrawals where initiator was unclear

AEs 2 (1.6%) 0 (0%) 0 (0%) 2 (3.0%) 0 (0.0%) 0 (0.0%) 2 (2.0%)Other 6 (4.5%) 0 (0%) 2 (6%) 4 (6.1%) 2 (3.0%) 1 (3.3%) 5 (4.9%)Not applicable 124 (93.9%) 17 (100%) 31 (94%) 60 (90.9%) 64 (97.0%) 29 (96.7%) 95 (93.1%)

IV = Intravenous; Anes. = Anesthesiology

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Supplementary Table 5Reporting participant withdrawals due to AEs


All trials (n=132)

Chronic (n=17)

Acute (n=33)


Pain journals(n=66)

Industry (n=30)

Other (n=102)

Report # or % of withdrawals due to AEs P=0.561 P=0.643 P=0.089

Separately for each arm 23 (17.4%) 4 (24%) 7 (21%) 10 (15.2%) 13 (19.7%) 10 (33.3%) 13 (12.7%)Separately for a selection of arms 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)

Globally for all arms 5 (3.8%) 1 (6%) 0 (0%) 2 (3.0%) 3 (4.5%) 1 (3.3%) 4 (3.9%)No withdrawals due to AEs occurred 72 (54.5%) 9 (53%) 17 (51%) 40 (60.6%) 32 (48.5%) 15 (50%) 57 (55.9%)

Withdrawals due to AEs not reported 31 (25.5%) 3 (18%) 9 (27%) 14 (21.2%) 17 (25.8%) 4 (13.3%) 27 (26.5%)

Report specific AEs causing withdrawal P=0.812 P=0.644 P=0.020

Yes, for all AE withdrawals 20 (15.2%) 4 (24%) 5 (15%) 10 (15.2%) 10 (15.2%) 5 (16.7%) 15 (14.7%)Yes, for selected AE withdrawals 5 (3.8%) 1 (6%) 1 (3%) 2 (3.0%) 3 (4.5%) 4 (13.3%) 1 (1.0%)

Specific AEs causing withdrawal not reported (not specified)

4 (3.0%) 0 (0%) 1 (3%) 0 (0.0%) 4 (6.0%) 2 (6.7%) 2 (2.0%)

No withdrawals due to AEs occurred 72 (54.5%) 9 (53%) 17 (51%) 40 (60.6%) 32 (48.5%) 15 (50%) 57 (55.9%)


Selected AEs causing withdrawalMet frequency cutoff or "common" AEs 0 (0.0%) 1 (6%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

SAEs 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)Differences between AEs per arm 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

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Treatment-emergent/-related 1 (0.8%) 0 (0%) 0 (0%) 1 (1.5%) 0 (0.0%) 1 (3.3%) 1 (1.0%)Not specified 3 (2.3%) 0 (0%) 1 (3%) 1 (1.5%) 2 (3.0%) 2 (6.7%) 1 (1.0%)Not applicable 127 (96.2%) 16 (94%) 32 (97%) 64 (97.0%) 63 (95.5%) 26 (86.7%) 100 (98.0%)

How report types of AEs causing withdrawal


Globally for all arms 6 (4.5%) 1 (6%) 0 (0%) 2 (3.0%) 4 (6.0%) 1 (3.3%) 5 (4.9%)Specific AEs causing withdrawal not reported 4 (3.0%) 0 (0%) 0 (0%) 0 (0.0%) 4 (6.0%) 2 (6.7%) 2 (2.0%)



Report AE withdrawals by severity 3 (2.3%) 1 (6%) 0 (0%) 1 (1.5%) 2 (3.0%) 1 (3.3%) 2 (2.0%)

Report AE withdrawals due to SAEs 10 (7.6%) 0 (0%) 3 (9%) 3 (4.5%) 7 (10.6%) 4 (13.3%) 6 (5.9%)

For each participant withdrawing due to AEs, were all AEs causing withdrawal reported

Yes, for all AE withdrawals 9 (6.8%) 3 (18%) 3 (9%) 5 (7.6%) 4 (6.1%) 3 (10.0%) 6 (5.9%)Yes, for some AE withdrawals 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)No 20 (15.2%) 2 (12%) 4 (12%) 7 (10.6%) 13 (16.7%) 6 (20.0%) 14 (13.7%)Specific AEs causing withdrawal not reported 4 (3.0%) 0 (0%) 0 (0%) 0 (0.0%) 4 (6.0%) 2 (6.7%) 2 (2.0%)



#: number; %: percent ; IV = Intravenous; Anes. = Anesthesiology

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Supplementary Table 6Reporting specific AEs


All trials (n=132)

Chronic (n=17)

Acute (n=33)


Pain journals(n=66)

Industry (n=30)

Other (n=102)

Report specific AEs P=0.014 P=0.010 P=0.195Yes, for all specific AEs 83 (62.9%) 7 (41%) 21 (64%) 48 (72.7%) 35 (53.0%) 20 (66.7%) 63 (61.8%)Yes, for selected specific AEs 15 (11.4%) 3 (18%) 1 (3%) 4 (6.1%) 11 (16.7%) 6 (20.0%) 9 (8.8%)No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Specific AEs not reported 15 (11.4%) 6 (35%) 3 (9%) 3 (4.5%) 12 (18.2%) 2 (6.7%) 13 (12.7%)

Selected specific AEsMet frequency cutoff or "common" AEs 10 (7.5%) 3 (18%) 1 (3%) 2 (3.0%) 8 (12.2%) 5 (16.7%) 5 (4.9%)

Differences in AEs per arm 1 (0.8%) 0 (0%) 0 (0%) 1 (1.5%) 0 (0.0%) 0 (0.0%) 1 (1.0%)Severe or moderate and severe 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Met cut off and differences in AEs per arm 1 (0.8%) 0 (0%) 0 (0%) 1 (1.5%) 0 (0.0%) 0 (0.0%) 1 (1.0%)

Treatment-emergent/-related 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Met cutoff/severe or moderate and severe AEs and treatment-emergent/-related

1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)

Not specified 2 (1.5%) 0 (0%) 0 (0%) 0 (0.0%) 2 (3.0%) 0 (0.0%) 2 (2.0%)Not applicable 117 (88.5%) 14 (82%) 32 (97%) 62 (93.9%) 55 (83.3%) 24 (80.0%) 93 (91.2%)

How report specific AEs# or % of pts experiencing each event per arm 85 (64.4%) 8 (47%) 21 (64%) 45 (68.2%) 40 (60.6%) 24 (80.0%) 61 (59.8%)

# or % of pts experiencing each event across arms 7 (5.3%) 1 (6%) 0 (0%) 3 (4.5%) 4 (6.0%) 1 (3.3%) 6 (5.9%)

Mean severity of each event per arm 2 (1.5%) 0 (0%) 1 (3%) 2 (3.0%) 0 (0.0%) 1 (3.3%) 1 (1.0%)

Mean severity of each event across arms 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)

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List of events per arm 2 (1.5%) 1 (6%) 0 (0%) 1 (1.5%) 1 (1.5%) 0 (0.0%) 2 (2.0%)List of events across arms 1 (0.8%) 0 (0%) 0 (0%) 1 (1.5%) 0 (0.0%) 0 (0.0%) 1 (1.0%)No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Specific AEs not reported 15 (11.4%) 6 (35%) 3 (9%) 3 (4.5%) 12 (18.2%) 2 (6.7%) 13 (12.7%)

Statistically compare specific AEs between arms P=0.053 P=0.099 P=0.012

Yes 70 (53.0%) 5 (29%) 16 (48%) 37 (56.1%) 33 (50.0%) 13 (43.3%) 57 (55.9%)No 28 (21.2%) 5 (29%) 6 (18%) 15 (22.7%) 13 (19.7%) 13 (43.3%) 15 (14.7%)No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Specific AEs not reported 15 (11.4%) 6 (35%) 3 (9%) 3 (4.5%) 12 (18.2%) 2 (6.7%) 13 (12.7%)

AE denominators per arm reported or clearly inferable P=0.094 P=0.062 P=0.130

Yes 91 (68.9%) 9 (53%) 19 (58%) 47 (71.2%) 44 (66.7%) 26 (86.7%) 65 (63.7%)No 7 (5.3%) 1 (6%) 3 (9%) 5 (7.6%) 2 (3.0%) 0 (0.0%) 15 (14.7%)No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Specific AEs not reported 15 (11.4%) 6 (35%) 3 (9%) 3 (4.5%) 12 (18.2%) 2 (6.7%) 13 (12.7%)

Separate expected & unexpected specific AEs 2 (1.5%) 1 (6%) 0 (0%) 0 (0.0%) 2 (3.0%) 0 (0.0%) 2 (2.0%)

Report method(s) to classify specific AEs as treatment-emergent

Yes, method specified 0 (0.0%) 2 (12%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Yes, method not specified 4 (3.0%) 0 (0%) 0 (0%) 1 (1.5%) 3 (4.5%) 2 (6.7%) 2 (2.0%)AEs not coded as treatment-emergent 94 (72.2%) 8 (47%) 22 (67%) 51 (77.3%) 43 (65.2%) 24 (80.0%) 70 (68.6%)

No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Specific AEs not reported 15 (11.4%) 6 (35%) 3 (9%) 3 (4.5%) 12 (18.2%) 2 (6.7%) 13 (12.7%)

Report method(s) to classify specific AEs as treatment-related adverse reactions

Yes, method specified 10 (7.2%) 4 (24%) 2 (6%) 5 (7.6%) 5 (7.6%) 7 (23.3%) 3 (2.9%)Yes, method not specified 7 (5.3%) 0 (0%) 0 (0%) 5 (7.6%) 2 (3.0%) 4 (13.3%) 3 (2.9%)

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AEs not coded as treatment-related adverse reactions 81 (61.4%) 6 (35%) 20 (61%) 42 (63.6%) 39 (59.1%) 15 (50%) 66 (64.7%)

No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Specific AEs not reported 15 (11.4%) 6 (35%) 3 (9%) 3 (4.5%) 12 (18.2%) 2 (6.7%) 13 (12.7%)

Report discontinuation or taper-emergent AEs 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)

Discontinuation or taper-emergent AEs assessed using standardized scale

1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)

Report distribution of the number of specific AEs experienced by participant

1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)

Specific AE severityReport any information about specific AE severity (mild, moderate, severe) P=0.110 P=0.607 P=0.071

Yes, for all specific AEs 11 (8.3%) 1 (6%) 1 (3%) 5 (7.6%) 6 (9.1%) 4 (13.3%) 7 (6.9%)Yes, for selected specific AEs 23 (17.4%) 2 (12%) 7 (21%) 14 (21.2%) 9 (13.6%) 8 (26.7%) 15 (14.7%)Yes, a general statement about overall AEs 15 (11.4%) 3 (18%) 0 (0%) 6 (9.1%) 9 (13.6%) 6 (20%) 9 (8.8%)

Yes, for selected specific AEs & general statement 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)

No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)Severity of specific AEs not reported 63 (47.7%) 10 (59%) 17 (52%) 30 (45.4%) 33 (50.0%) 10 (33.3%) 53 (52.0%)

Selected specific AEs reported by severity

Met frequency cutoff or "common" AEs 2 (1.5%) 0 (0%) 1 (3%) 1 (1.5%) 1 (1.5%) 0 (0.0%) 2 (2.0%)

Met frequency cutoff and differences in AEs per arm 1 (0.8%) 0 (0%) 1 (3%) 1 (1.5%) 0 (0.0%) 0 (0.0%) 1 (1.0%)

Severe or moderate and severe 7 (5.3%) 2 (12%) 1 (3%) 4 (6.0%) 3 (4.5%) 5 (16.7%) 2 (2.0%)

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Only occurred during study period 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Treatment-emergent/-related 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Other 6 (4.5%) 0 (0%) 2 (6%) 5 (7.6%) 1 (1.5%) 1 (3.3%) 5 (4.9%)Not specified 7 (5.3%) 0 (0%) 2 (6%) 3 (4.5%) 4 (6.1%) 2 (6.7%) 5 (4.9%)Not applicable 109 (82.6%) 15 (88%) 26 (79%) 52 (78.8%) 57 (86.4%) 22 (73.3%) 87 (85.3%)

Report number or percent of mild, moderate, severe AEs


Globally for all arms 7 (5.3%) 1 (6%) 0 (0%) 1 (1.5%) 6 (9.1%) 3 (10.0%) 4 (3.9%)#/% of mild, moderate, severe AEs not reported 27 (20.5%) 0 (0%) 0 (0%) 13 (19.7%) 14 (21.2%) 10 (33.3%) 17 (16.7%)

No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)AEs not reported by severity 63 (47.7%) 15 (88%) 21 (64%) 30 (45.4%) 33 (50.0%) 10 (33.3%) 53 (52.0%)

Report number or percent of participants experiencing severe or moderate & severe AEs

P=0.502 P=0.405 P=0.040


Globally for all arms 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)None occurred 13 (9.8%) 0 (0%) 1 (3%) 6 (9.1%) 7 (10.6%) 5 (16.7%) 8 (7.8%)#/% of pts experiencing severe, moderate & severe AEs not reported

20 (15.2%) 0 (0%) 0 (0%) 8 (12.1%) 12 (18.2%) 10 (33.3%) 17 (16.7%)

No AEs occurred 19 (14.4%) 1 (6%) 8 (24%) 11 (16.7%) 8 (12.1%) 2 (6.7%) 17 (16.7%)AEs not reported by severity 63 (47.7%) 15 (88%) 21 (64%) 30 (45.4%) 33 (50.0%) 10 (33.3%) 53 (52.0%)

Statistically compare AE severity between arms 17 (12.9%) 0 (0%) 7 (21%) 11 (16.7%) 6 (9.1%) 4 (13.3%) 13 (12.7%)

#: number; %: percent; IV = Intravenous; Anes. = Anesthesiology

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Supplementary Table 7Reporting SAEs


All trials (n=132)

Chronic (n=17)

Acute (n=33)


Pain journals(n=66)

Industry (n=30)

Other (n=102)

Report any information on SAEs P=0.202 P=0.851 P<0.01Yes 9 (6.8%) 2 (12%) 0 (0%) 4 (6.1%) 5 (7.6%) 7 (23.3%) 2 (2.0%)No SAEs occurred 42 (31.8%) 5 (29%) 10 (30%) 20 (30.3%) 22 (33.3%) 11 (36.7%) 31 (30.4%)No information on SAEs reported 81 (61.4%) 10 (59%) 23 (70%) 42 (63.6%) 39 (59.1%) 12 (40.0%) 69 (67.6%)

Specific SAEs reportedYes, for all specific SAEs 6 (4.5%) 1 (6%) 0 (0%) 4 (6.1%) 2 (3.0%) 5 (16.7%) 1 (1.0%)Yes, for selected SAEs 2 (1.5%) 1 (6%) 0 (0%) 0 (0.0%) 2 (3.0%) 1 (3.3%) 1 (1.0%)Specific SAEs not reported 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)No SAEs occurred 42 (31.8%) 5 (29%) 10 (30%) 20 (30.3%) 22 (33.3%) 11 (36.7%) 31 (30.4%)No information on SAEs reported 81 (61.4%) 10 (59%) 23 (70%) 42 (63.6%) 39 (59.1%) 12 (40.0%) 69 (67.6%)

Selected SAEsMet frequency cutoff or "common" SAEs 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Differences in SAEs per arm 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 0 (0.0%) 1 (1.0%)Not specified 1 (0.8%) 1 (6%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)Not applicable 130 (98.4%) 16 (94%) 33 (100%) 66 (100%) 64 (97.0%) 29 (96.7%) 101 (99.0%)

How report specific SAEsSeparately for each arm 7 (5.3%) 1 (6%) 0 (0%) 4 (6.1%) 3 (4.5%) 5 (16.7%) 2 (2.0%)Separately for a selection of arms 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Globally for all arms 1 (0.8%) 1 (6%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)Specific SAEs not reported 1 (0.8%) 0 (0%) 0 (0%) 0 (0.0%) 1 (1.5%) 1 (3.3%) 0 (0.0%)No SAEs occurred 42 (31.8%) 5 (29%) 10 (30%) 20 (30.3%) 22 (33.3%) 11 (36.7%) 31 (30.4%)No information on SAEs 81 (61.4%) 10 (59%) 23 (70%) 42 (63.6%) 39 (59.1%) 12 (40.0%) 69 (67.6%)

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reported

How report # or % of participants experiencing SAEs

#/% of pts with SAEs per arm 2 (1.5%) 0 (0%) 0 (0%) 1 (1.5%) 1 (1.5%) 1 (3.3%) 1 (1.0%)#/% of pts with SAEs across arms 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

#/% of pts with SAEs not reported 7 (5.3%) 2 (12%) 0 (0%) 3 (4.5%) 4 (6.1%) 6 (20.0%) 1 (1.0%)

No SAEs occurred 42 (31.8%) 5 (29%) 10 (30%) 20 (30.3%) 22 (33.3%) 11 (36.7%) 31 (30.4%)No information on SAEs reported 81 (61.4%) 10 (59%) 23 (70%) 42 (63.6%) 39 (59.1%) 12 (40.0%) 69 (67.6%)

For each participant experiencing SAEs, were specific SAEs reported

Yes, for all specific SAEs 2 (1.5%) 0 (0%) 0 (0%) 1 (1.5%) 1 (1.5%) 1 (3.3%) 1 (1.0%)Yes, for selected SAEs 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Specific SAEs not reported 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Pts with SAEs not reported 7 (5.3%) 2 (12%) 0 (0%) 3 (4.5%) 4 (6.1%) 6 (20.0%) 1 (1.0%)No SAEs occurred 42 (31.8%) 5 (29%) 10 (30%) 20 (30.3%) 22 (33.3%) 11 (36.7%) 31 (30.4%)No information on SAEs reported 81 (61.4%) 10 (59%) 23 (70%) 42 (63.6%) 39 (59.1%) 12 (40.0%) 69 (67.6%)

How report each participant’s specific SAEs

#/% of pts with specific SAEs per arm 2 (1.5%) 0 (0%) 0 (0%) 1 (1.5%) 1 (1.5%) 1 (3.3%) 1 (1.0%)

#/% of pts with specific SAEs across arms 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Specific SAEs not reported 0 (0.0%) 0 (0%) 0 (0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)Pts with SAEs not reported 7 (5.3%) 2 (12%) 0 (0%) 3 (4.5%) 4 (6.1%) 6 (20.0%) 1 (1.0%)No SAEs occurred 42 (31.8%) 5 (29%) 10 (30%) 20 (30.3%) 22 (33.3%) 11 (36.7%) 31 (30.4%)No information on SAEs reported 81 (61.4%) 10 (59%) 23 (70%) 42 (63.6%) 39 (59.1%) 12 (40.0%) 69 (67.6%)

#: number; %: percent; IV = Intravenous; Anes. = Anesthesiology

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