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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dickenson, A. H. Dray, A. |
| Description | Author Affiliation: Dickenson AH ( Department of Pharmacology, University College, London.) |
| Abstract | 1. Capsazepine has recently been described as a competitive capsaicin antagonist. We have used this compound to test the hypotheses that the in vitro and in vivo effects of capsaicin are due to interactions with a specific receptor. 2. In an in vitro preparation of the neonatal rat spinal cord with functionally connected tail, the activation of nociceptive afferent fibres by the application of capsaicin, bradykinin or noxious heat (48 degrees C) to the tail could be measured by recording a depolarizing response from a spinal ventral root. Application of capsaicin or substance P to the spinal cord also evoked a depolarizing response which was recorded in a ventral root. 3. When capsazepine (50 nM-20 microM) was administered to the tail or spinal cord it did not evoke any measurable response. However on the tail, capsazepine reversibly antagonized (IC50 = 254 +/- 28 nM) the responses to capsaicin but not to heat or bradykinin administered to the same site. Similarly capsazepine administration to the spinal cord antagonized the responses evoked by capsaicin (IC50 = 230 +/- 20 nM) applied to the cord but not responses evoked by substance P on the cord or by noxious heat and capsaicin on the tail. 4. In halothane anaesthetized rats, C-fibre responses evoked by transcutaneous electrical stimulation of the receptive field were recorded from single wide dynamic range neurones located in the spinal dorsal horn. C-fibre evoked discharges were consistently reduced by the systemic administration of capsaicin (20 mumol kg-1, s.c.) and this action of capsaicin was antagonized by capsazepine (100 mumol kg-1) administered by the same route. In addition the systemic effect of capsaicin was antagonized by a spinal intrathecal administration of capsazepine (5-50 nmol). 5. Intradermal injections of capsaicin, localized to the peripheral receptive field, usually one toe of the ipsilateral hind-paw, produced a transient increase in C-fibre-evoked activity followed by a prolonged period of localized insensitivity to transcutaneous C-fibre stimulation. These effects of capsaicin were significantly reduced by the concommitant administration of capsazepine to the same site. 6. These data demonstrate that capsazepine is a selective antagonist of capsaicin on nociceptive neurones in vitro and in vivo and suggest that the effects of capsaicin were mediated by activation of a specific receptor. Since the antinociceptive effect produced by systemically administered capsaicin was antagonised by spinal intrathecal capsazepine this further supports the hypothesis that capsaicin exerts its antinociceptive effect by acting on specific receptors localized to sensory nerve fibres in the spinal cord. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 104 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1991-12-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Analgesics Pharmacology Capsaicin Analogs & Derivatives Antagonists & Inhibitors Receptors, Drug Spinal Cord Metabolism Animals Bradykinin Electric Stimulation In Vitro Techniques Injections, Spinal Nerve Fibers Drug Effects Spinal Nerve Roots Physiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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