title: Inhibition of spinal nociceptive responses after intramuscular injection of capsaicin involves activation of noradrenergic and opioid systems.
abstract: Extracellular recordings of wide dynamic range neurones in the dorsal horn driven by electrical stimulation of the sciatic nerve were performed in intact urethane-anaesthetized Sprague-Dawley rats. The electrically evoked neuronal responses were defined as A- and C-fibres responses according to latencies, and the effect of a deep nociceptive conditioning stimulus induced by 200 microg capsaicin (8-methyl-N-vanillyl-6-noneamide) injected into the contralateral gastrocnemius-soleus muscle was studied for at least 30 min. Independent of the size and location of the receptive field of the neurone under study, a clear inhibition of the neuronal responses was observed. The electrically evoked C-fibre responses were inhibited to 53% of baseline 15-30 min after injection of capsaicin. This inhibition was only slightly attenuated by 125 nmol of the alpha-adrenoceptor antagonist phentolamine or 250 nmol of the opioid receptor antagonist naloxone applied directly onto the spinal cord when the two compounds were administered separately 5 min before capsaicin. In contrast, when a mixture of the two compounds was given 5 min before capsaicin, the effect of capsaicin was completely abolished. These results indicate that activation of the capsaicin-sensitive afferents in the gastrocnemius-soleus muscle inhibits the electrically evoked C-fibre responses in the dorsal horn by activating noradrenergic and opioidergic inhibitory systems. Moreover, our data indicate that the activation of these two systems following injection of capsaicin has a sub-additive inhibitory effect on the wide dynamic range neurones in the spinal cord. We conclude that only one of these systems is sufficient for the inhibition to occur.
authors.affiliation: Department of Physiology, University of Bergen, Arstadveien 19, N-5009, Bergen, Norway. johannes.gjerstad@pki.uib.no
authors.forename: J
authors.initials: J
authors.lastname: Gjerstad
authors.forename: A
authors.initials: A
authors.lastname: Tjølsen
authors.forename: F
authors.initials: F
authors.lastname: Svendsen
authors.forename: K
authors.initials: K
authors.lastname: Hole
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D018847:Opioid Peptides; D002211:Capsaicin; D009638:Norepinephrine; D010646:Phentolamine