Abstract
Intrathecally administered cholinergic agonists such as oxotremorine (muscarinic), carbachol (mixed nicotinic and muscarinic agonist), and epibatidine (nicotinic) have all been shown to reduce nociception in behavioral studies. Thus, there is substantial evidence for a role of acetylcholine (ACh) in the control of nociception in the spinal cord, but the mechanisms regulating ACh release are not known. The present study was initiated to establish a rat model to study which mechanisms are involved in the control of ACh release. Spinal microdialysis probes were inserted intraspinally at the C1–C5 spinal level in isoflurane-anesthetized rats. The probes were perfused with Ringer's solution containing 10 μM neostigmine to prevent degradation of ACh. Oxotremorine, carbachol, epibatidine, and scopolamine, dissolved in Ringer's solution, were administered intraspinally via dialysis and 30 μl/10-min samples of dialysate were collected for HPLC analysis of ACh content. The release of ACh was found to be constant in the control (Ringer's only) situation during the experimental period of 150 min. Oxotremorine (100–1000 μM), carbachol (1 mM), and epibatidine (50–5000 μM) enhanced but scopolamine (50–200 nM) decreased the intraspinal release of ACh. Oxotremorine (ED50 = 118 μM) and epibatidine (ED50 = 175 μM) were found to produce a dose-dependent increase of ACh release. Cholinergic agonists caused an increase of intraspinal ACh and the antagonist scopolamine caused a decreased release of ACh. The data do not support an autoreceptor function of either nicotinic or muscarinic receptors in the spinal cord, contrary to what has been observed in the brain.
Footnotes
-
Send reprint requests to: A. U. Höglund, Department of Physiology, Biomedical Center, Box 572, Uppsala University, S-751 23 Uppsala, Sweden. E-mail: urban.hoglund{at}bmc.uu.se
-
↵1 This study was at an initial state supported by National Institutes of Health Grants HL-57120 and K98-04R-12790. The work also was supported by The Swedish Medical Research Council (K98-04R-12790) and Swedish Match (200006).
- Abbreviations:
- mAChR
- muscarinic acetylcholine receptor
- Received April 21, 2000.
- Accepted June 9, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|