Nicotine Antinociception: Possible Role for Ca 2+

Transcription

1 World Journal of Medical Sciences (2): 9-23, 26 ISSN 87-3 IDOSI Publications, 26 Nicotine Antinociception: Possible Role for Ca 2 G.F. Ibironke, A.S. Oyadeyi and K.I. Ajiboye Dept of Physiology, College of Medicine, University of Ibadan, Nigeria 2 Department of Physiology, Ladoke Akintola, University of Technology, P.M.B. 4, Ogbomoso, Nigeria Abstract: The present study was designed to determine the degree of participation of calcium ions in the antinociception produced by systemic nicotine. Adult male Wistar rats (8-22 g) pretreated with saline ( ml kg ) or calcium channel blockers, verapamil or nifedipine (.-.2 mg kg each) were injected with nicotine ( mg kg ) min later. The animals were subjected to the hot plate test after another 3 min. Hot plate latencies (HPL) were measured before (base line) and at, 3, 4 and 6 min after nicotine injection. Nicotine produced antinociception for to 4 min peaking 3 min after injection. Intraperitoneal (i.p) administration of graded doses of nifedipine and verpamil each antagonized in part, the antinociception produced by nicotine. Systemic administration of the vehicle ( ml kg ) did not alter nicotine-induced antinociception. The data suggest that the antinociceptive responses produced by nicotine are mediated at least in part via the calcium ions. Key words: Antinociception calcium verapamil nifedipine nicotine INTRODUCTION level and their activation produces antinociception mainly through the release of dopamine [3], noradrenaline [4], The management and treatment of pain is acetylcholine [], glutamate [6] and GABA [7]. Although probably one of the most common and yet most difficult nicotine antinociception may not extend to all types of aspects of medical practice. Analgesic therapy is currently pain and it appears to be dependent on the mode of dominated by two major classes of analgesic drugs, administration, recent observations suggest that cigarette namely opioids and the non-steroidal anti-inflammatory smoking and nicotine reduce pain in humans indlicating drugs (NSAIDs). Many improved synthetic variants, as a true analgesic component [8-]. well as techniques of administration have been developed However the data in human clinical literature on the but there is considerable opportunity for conceptual relationship between nicotine and pain are inconclusive innovation. Both classes of analgesic drugs produce at best. Nicotine antinociception has been shown to side effects, such as gastrointestinal disturbances and involve several systems and receptors, for example the renal damage (with NSAIDs), respiratory depression and cholinergic system [2-4] and the endogenous opioid possibly dependence (with opioids). It is obvious that system []. In view of the recent observations in our new models designed as analgesic agents are needed, laboratory on the diverse pharmacological and hence research into nicotine antinociception physiological activities of nicotine, this study was Nicotine is one of the active components in designed to probe further into the receptor basis of tobacco smoke and it appears to play a major role in nicotine antinociception using the calcium channel tobacco addiction []. This compound affects different blockers, nifedipine and verapamil. aspects of behaviour such as locomotion, nociception, anxiety, learning and memory and it produces MATERIALS AND METHODS several behavioural responses related to its addictive properties such as rewarding effects and physical Animals: Adult male albino Wistar rats (8-2 g) dependence [2]. obtained from the central animal house, College of The pharmacological effects of nicotine are mediated Medicine Univeristy of Ibadan were used throughout the by the activation of nicotine acetylcholine receptors study. The animals were housed in groups of six where (nachr S) which are located mainly at the presynaptic they had free access to food and water. Corresponding Author: Dr. G.F. Ibironke, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria 9

2 World J. Med. Sci., (2): 9-23, 26 Drugs: Nicotine was obtained from DBH chemicals RESULTS Ltd. (Poole, England). Nifedipine and verapamil were purchased from a local pharmaceutical outfit in the city of Effect of saline pre-treatment on nicotine Ibadan, Nigeria. antinociception: Figure shows that normal saline administered min before nicotine had no significant Hot plate test: The original method of Eddy and effect on nicotine antinociceptive activity as the two Leimbach [6] as modified by Ibironke et al. [7] was curves, nicotine alone and nicotine with saline were employed. The hot plate temperature was maintained at almost superimposed on each other. 2 ± 2. C and a cut off time of 6 sec was imposed to avoid significant tissue damage. Pain sensitivity was Effect of nifedipine pre-treatment on nicotine evaluated by the response latency for paw licking on the antinociception: It was observed that graded doses of hot plate. nifedipine produced a dose-dependent inhibition of For the purpose of the experiment, the animals were nicotine antinociception (Fig. 2). divided into 3 groups of 8 rats each and treated as follows. Effect of verapamil pre-treatment on nicotine antinociception: The results were similar to that of Group I: Normal saline (i.p, ml kg ) + Nicotine nifedipine as verapamil, also dose dependently inhibited (i.v, mg lkg ) min later. antinociceptive acitivity of nicotine (Fig. 3). Group II: Nifedipine (i.p,.-.2 mg kg ) + Nicotine (i.v, mg kg ) min later. DISCUSSION Group III: Verapamil (i.p,.-.2 mg kg ) + Nicotine (i.v, mg kg ) min later. The results presented herein support previous findings from our laboratory (unpublished observations) About 3 min after the administration of nicotine, that nicotine has potent antinociceptive properties. A the animals were placed on the hot plate and latencies similar profile has been reported by other investigators were measured at min intervals for the next one using other nicotine agents [8-2]. The mechanism of hour. nicotine antinociception has been a subject of investigation by various authors. For example, Statistical analysis: Values were expressed, as means ± mecamylamine a tertiary nicotinic blocker known to block S.E.M. Statistical significance was determined using the the central and peripheral effects of nicotine antagonized students t-test. Values with p<. were considered the antinociceptive effect completely [2] indicating the significant. involvement of nicotinic receptors. Phan et al. [4] found Nicotine + normal saline Fig. : Antinociceptive effects of nicotine with or without normal saline. Each data point represents the mean ± S.E.M of nine rats 2

3 World J. Med. Sci., (2): 9-23, Latency (sec) Nicotine +. mg kg nifedipine Nicotine +. mg kg nifedipine Nicotine +.3 mg kg nifedipine Fig. 2: Effects of graded doses of nifedipine on nicotine antinociception. Each point represents the mean ± the S.E.M of ten rats 4 4 Latency (sec) Nicotine +. mg kg nifedipine Nicotine +. mg kg nifedipine Nicotine +.3 mg kg nifedipine Fig. 3: Effects of graded doses of verapamil on nicotine antinociception. Each point represents the mean ± the S.E.M of seven rats 2

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