Inhibition of spinal nociceptive responses after intramuscular injection of capsaicin involves activation of noradrenergic and opioid systems

Extracellular recordings of wide dynamic range neurones in the dorsal horn driven by electrical stimulation of the sciatic nerve were performed in int act urethane-anaesthetized Sprague-Dawley rats. The electrically evoked neu ronal responses were defined as A- and C-fibres responses according to late ncies, and the effect of a deep nociceptive conditioning stimulus induced b y 200 mu g capsaicin (8-methyl-N-vanillyl-6-noneamide) injected into the co ntralateral gastrocnemius-soleus muscle was studied for at least 30 min. In dependent of the size and location of the receptive field of the neurone un der study, a clear inhibition of the neuronal responses was observed. The e lectrically evoked C-fibre responses were inhibited to 53% of baseline 15-3 0 min after injection of capsaicin. This inhibition was only slightly atten uated by 125 nmol of the alpha-adrenoceptor antagonist phentolamine or 250 nmol of the opioid receptor antagonist naloxone applied directly onto the s pinal cord when the two compounds were administered separately 5 min before capsaicin. In contrast. when a mixture of the two compounds was given 5 mi n before capsaicin, the effect of capsaicin was completely abolished. These results indicate that activation of the capsaicin-sensitive afferents in t he gastrocnemius-soleus muscle inhibits, the electrically evoked C-fibre re sponses in the dorsal horn by activating noradrenergic and opioidergic inhi bitory systems. Moreover, our data indicate that the activation of these tw o systems following injection of capsaicin has a sub-additive inhibitory ef fect on the wide dynamic range neurones in the spinal cord. We conclude tha t only one of these systems is sufficient fur the inhibition to occur. (C) 2000 Published by Elsevier Science B.V. All rights reserved.