RESUMEN
The neurovascular responses to noxious electrically evoked axon reflex (EAR) stimulation and iontophoretic application of endothelium-dependent [acetylcholine (ACh)] and independent [sodium nitrite (NaNO2)] vasodilator substances were examined in human forearm skin using laser Doppler flowmetry, before and after repeated topical applications of the neurotoxin capsaicin (chronic capsaicin pre-treatment). Following 3 or 4 days of capsaicin pre-treatment the normal vasodilator response to acute application of capsaicin was significantly reduced as was the EAR response. There were, however, no significant changes in the vasodilator responses to either ACh or NaNO2, suggesting that the neurogenic axon reflex is in series with the endothelial and microvascular smooth muscle mechanisms of vasodilatation. Recovery of normal EAR occurred within 2-4 weeks of cessation of capsaicin pre-treatment.
Asunto(s)
Capsaicina/farmacología , Piel/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Adulto , Estimulación Eléctrica , Femenino , Humanos , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Piel/irrigación sanguínea , Sistema Vasomotor/efectos de los fármacosRESUMEN
Hyperalgesia and allodynia, lasting for months or even years, occurs in the form of post-herpetic neuralgia in approximately 70% of adults previously infected with the varicella herpes zoster virus. The present study aimed at testing the analgesic desensitising actions and reversibility of repeated application of topical capsaicin on disordered polymodal nociceptors and peptidergic sensory fibres mediating warm and pain sensation. Cutaneous nociceptor desensitisation was measured using the Glasgow automated thermal threshold test (Medelec TTT). For normal subjects (n = 69) the mean forearm warm threshold was 0.15 +/- 0.07 degrees C and the cold threshold was 0.14 +/- 0.10 degrees C. A variable degree of partial desensitisation of herpes-affected skin was found in 15 patients with post-herpetic neuralgia before capsaicin treatment where the mean threshold elevation for warm detection was 1.19 degrees C and 0.7 degrees C for cold detection, compared with the corresponding normal skin. In preliminary studies of 15 patients with post-herpetic neuralgia, good pain relief averaging 30% or 77% occurred in the affected dermatome(s) after 3 to 4 weeks of 0.01% or 0.05% capsaicin cream respectively, applied 3-4 times daily. The warm thresholds, after chronic capsaicin treatment, increased between 0.1 and 7.60 degrees C, the average elevation being 3.69 degrees C. By contrast cold thresholds after capsaicin altered inconsistently and by only an average of 0.08 degrees C. The results suggest that elevation of the warm threshold may indicate the desensitisation achieved by capsaicin treatment of skin polymodal nociceptors. Cold detection, being dependent upon A-delta cold fibre function, is unaffected by capsaicin treatment. There was a poor correlation between pain relief and elevation of warm detection in response to capsaicin treatment. Generally, it was found that those patients with less initial desensitisation to warm detection as a consequence of post-herpetic neuralgia experienced better pain relief after capsaicin was applied. The method used permits determination of the minimum effective desensitising dose of capsaicin, enables patient compliance and progress to be monitored and should allow the prediction of patients likely to achieve the best response to treatment.