Denervazione-deafferentazione

The terms “denervation” and “deafferentation” are

frequently confused and misused; they do not mean the

same thing.

2

Devor, M. (2006). Response of nerves to injury in relation to neuropathic pain. Chapter 58. In S. L. McMahon & M. Koltzenburg (Eds.), Wall and Melzack’s textbook of pain (5th ed., pp. 905–927). London: Churchill Livingstone.

Denervation in the present context refers to severing sensory axons that

innervate the limb. Sensory endings rapidly degenerate in the process of

anterograde (Wallerian) degeneration. However, sensory cell bodies in the

DRG, their connectivity with the spinal cord, and the ability of (ectopically

generated) afferent impulses to reach the CNS are largely preserved.

3

Deafferentation refers to blocking the arrival of afferent impulses into the

CNS by severing dorsal roots (Dorsal Rhizotomy). The sensory neurons in the

dorsal root ganglion (DRG) mostly survive, as do sensory endings in the skin.

The limb is not denervated. It is very likely that pain due to denervation and

deafferentation results from different mechanisms (Devor 2006).

5

Pain and autotomy after nerve injury is probably due to

abnormal spontaneous afferent discharge generated

ectopically at the nerve injury site, and in axotomized DRG

neurons. There might also be a contribution by residual intact

neurons that continue to innervate adjacent skin. The ectopic

firing plays two roles. First, it constitutes a primary

nociceptive afferent signal. Second, it probably triggers

central sensitization in the spinal cord dorsal horn, and

perhaps also in the brain. The sensitized CNS amplifies and

augments pain sensation due to the spontaneous afferent

discharge. It also renders light tactile input from residual

neighboring afferents painful, yielding tactile allodynia in the

skin bordering on the denervated zone (Defrin et al. 1996;

Devor 2006).

6

Pain and autotomy after deafferentation must be due to

another mechanism as dorsal rhizotomy does not trigger

massive ectopia in axotomized afferents, and even if it did, the

impulses would have no access to the CNS. Pain following

rhizotomy is, therefore, presumed to be due to impulses that

originate within the deafferented CNS itself. Deafferentation

triggers many structural and neurochemical changes in the CNS,

and abnormal bursting discharges have been recorded in

deafferented spinal dorsal horn in animals and in humans. The

possibility that deafferentation pain is indeed due to this activity

is supported by the observation that surgical destruction of the

abnormal dorsal horn tissue by DREZotomy often relieves this

type of pain (Rossitch et al. 1993; Guenot et al. 2002). ???????????????????

Denervazione

7

Dolore neuropatico periferico Spontaneo ed evocato

DENERVAZIONE Dolore neuropatico periferico Da patologia o lesione delle fibre dai tessuti al ganglio

La deafferentazione termo-nocicettiva e il dolore neuropatico

centrale “da deafferentazione”

9

Dolore spontaneo

Buonocore

Il dolore nasce dai neuroni per iperattività da denervazione del II° neurone

Deafferentazione del II° neurone per lesione del I° neurone sensitivo

fibre termo-dolorifiche Adelta e C

Buonocore

Avulsione del plesso brachiale

Sensory loss in avulsion of

C5-T1. C4

innervates the skin of the

outer aspect of the shoulder;

T2 innervates the skin of the

inner aspect of the arm

15

Dolore spontaneo (mai evocato) all’avambraccio e alla mano sia in forma di bruciore che di morsa in una zona completamente addormentata (anestesia dolorosa)

Buonocore

Deafferentazione del III° neurone

Buonocore

LESIONI MIDOLLARI

PERDITA DELLE SENSIBILITA’ TERMO-DOLORIFICHE E TATTILI PROPRIOCETTIVE

PERDITA DELLE SENSIBILITA’ TERMO-DOLORIFICA

DEAFFERENTAZIONE CORTICALE

Central post stroke pain

21

Deafferentation Pain

Central Pain

Central Neuropathic

Pain

Anesthesia dolorosa

Thalamic pain

Central pain Dolore che origina nel SNC

22

Central neuropathic pain Dolore ectopico che origina per lesione della via

somatosensoriale centrale

Deafferentation pain Dolore che origina per interruzione della via

termo-nocicettiva tra i neuroni

Considerazioni finali

IL DOLORE IN MOLTE FORME CLINICHE E’ UN DOLORE DA DEAFFERENTAZIONE

I LIVELLI DI DEAFFERENTAZIONE LNGO LA VIA TERMO-NOCICETTIVA

• IL DOLORE DA DEAFFERENTAZIONE E’ SEMPRE SPONTANEO

• SI PRESENTA IN AREE DI ASSENZA DI SENSIBILITA’ TATTILE – DOLORIFICA

• L’ESTENSIONE DELL’AREA E’ MINORE RISPETTO ALL’AREA DI DANNO NEUROLOGICO

• IL DOLORE E’ SEMPRE PROFONDO A VOLTE DESCRITTO COME BRUCIORE E A VOLTE COME MORSA, COSTRIZIONE O ESPLOSIONE

• SCOMPARE CON IL SONNO E SI RIDUCE SENSIBILMENTE IN MOMENTI DI DISTRAZIONE

• AUMENTA CON L’EMOZIONE E GLI EVENTI NEGATIVI

• NON SI ACCOMPAGNA MAI AD ALLODINIA E A IPERALGESIA