1. Activation of neurokinin receptors contributes to the excitation of many dorsal horn neurons by cutaneous sensory stimuli, particularly noxious stimuli. In the present study we investigate the role of neurokinin receptors in the activation of primate spinothalamic tract (STT) neurons by cutaneous mechanical stimuli and by intradermal injection of capsaicin. This was done by testing the responses of these neurons to a battery of cutaneous stimuli before and during infusion by microdialysis of antagonists selective for NK1 and NK2 receptors. 2. The NK1 receptor antagonists cis-3-(2-methoxybenzyl-amino-2-benzhydrylquinuclidine (CP96345) and D-Pro9-[Spiro-y-lactam]-Leu10,Trp11)-Physalaemin(1-11) (GR82334) did not significantly reduce the responses of STT cells to mechanical stimulation of the skin. Both NK1 antagonists did, however, produce a significant reduction in the responses of STT neurons to an intradermal injection of capsaicin. Finally, despite having no effects on responses to mechanical stimuli, both NK1 antagonists prevented the sensitization of the responses to cutaneous stimuli that is usually observed after intradermal injections of capsaicin. 3. The NK2 selective antagonists PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (GR98400) and [Tyr5,D-Trp6,8,9,Lys10]-NKA (4-10) (MEN10376) had effects very similar to those of the NK1 antagonists, but with an important difference. Neither NK2 antagonist affected the responses of STT neurons to noxious or innocuous mechanical stimulation of the skin, but they did reduce the responses to intradermal capsaicin injections. These compounds failed to prevent capsaicin-induced sensitization. In fact, cells exposed to GR98400 or MEN10376 showed unusually sustained increases in the responses to mechanical stimuli after the first capsaicin injection, suggesting that these compounds actually induced sensitization. 4. These results support the contention that both neurokinin receptors participate in the processing of nociceptive information in the dorsal horn, especially responses to strong stimuli such as intradermal injection of capsaicin. NK1 receptors are also involved in the sensitization of STT neurons after peripheral injury. A clearer understanding of the role of NK2 receptors in sensitization requires further studies with improved antagonists.

• MeSH
• antagonisté neurokininových receptorů typu 1 MeSH
• bifenylové sloučeniny farmakologie   MeSH
• fysalemin analogy a deriváty   farmakologie   MeSH
• injekce intradermální MeSH
• kapsaicin * farmakologie   MeSH
• kůže * inervace   MeSH
• Macaca fascicularis MeSH
• mechanoreceptory účinky léků   MeSH
• nervový přenos fyziologie   účinky léků   MeSH
• neurokinin A analogy a deriváty   farmakologie   MeSH
• neurony fyziologie   účinky léků   MeSH
• nociceptory * fyziologie   účinky léků   MeSH
• peptidové fragmenty farmakologie   MeSH
• práh bolesti účinky léků   MeSH
• receptory neurokininu-1 * fyziologie   MeSH
• receptory neurokininu-2 * antagonisté a inhibitory   fyziologie   MeSH
• spinální ganglia fyziologie   účinky léků   MeSH
• tractus spinothalamicus * fyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH