Skip to main content
Log in

Antinociceptive effect of nicotine in various pain models in the mouse

  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The antinociceptive effect of nicotine administered intracereboventricularly (i.c.v.) or intrathecally (i.t) in several pain models was examined in the present study. We found that i.t. treatment with nicotine (from 5 to 20 g) dose-dependently blocked pain behavior revealed during the second phase, but not during the first phase in the formalin test. In addition, i.c.v. treatment with nicotine (from 0.1 to 10 μg) dose-dependently attenuated pain behavior revealed during both the first and second phases. In addition to the formalin test, nicotine administered i.c.v. or i.t. attenuated acetic acid-induced writhing response. Furthermore, i.c.v. or i.t. administration of nicotine did not cause licking, scratching and biting responses induced by substance P, glutamate, TNF-α (100 pg), IL-1β (100 pg) and INF-γ (100 pg) injectied i.t. The antinociception induced by supraspinally-administered nicotine appears to be more effective than that resulting from spinally administered nicotine. Our results suggest that nicotine administration induces antinociception by acting on the central nervous system and has differing antinociceptive profiles according to the various pain models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abbott, F., Franklin, K., Ludwick, R., and Melzack, R., Apparent lack of tolerance in the formalin test suggests different mechanisms for morphine analgesia in different types of pain.Pharmacol. Biochem. Behav., 15, 637 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Aceto, M. D., Bagley, R. S., Dewey, W. L., Fu, T. C., and Martin, B. R., The spinal cord as a major site for the antinociceptive action of nicotine in the rat.Neuropharmacology, 25, 1031 (1986).

    Article  PubMed  CAS  Google Scholar 

  • Ahmadiani, A., Hosseiny, J., Semnanian, S., Javan, M., Saeedi, F., Kamalinejad, M., and Saremi, S., Antinociceptive and anti-inflammatory effects of Elaeagnus angustifolia fruit extract.J. Ethnopharmacol., 72, 287 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Bannon, A. W., Decker, M. W., Kim, D. J., Campbell, J. E., and Arneric, S. P., ABT-594, a novel cholinergic channel modulator, is efficacious in nerve ligation and diabetic neuropathy models of neuropathic pain.Brain Res., 801, 158 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Benowitz, N. L. and Jacob, P. 3rd, Nicotine metabolism in nonsmokers.Clin. Pharmacol. Ther., 48, 473 (1990).

    PubMed  CAS  Google Scholar 

  • Castane, A., Valjent, E., Ledent, C., Parmentier, M., Maldonado, R., and Valverde, O., Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence.Neuropharmacology, 43, 857 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Choi, S. S., Lee, J. K., and Suh, H. W., Antinociceptive profiles of aspirin and acetaminophen in formalin, substance P and glutamate pain models.Brain Res., 921, 233 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Chung, K. M., Lee, K. C., Choi, S. S., and Shu, H. W., Differential roles of spinal cholera toxin- and pertussis toxin-sensitive G proteins in nociceptive responses caused by formalin, capsaicin, and substance P in mice.Brain Res. Bull., 537 (2001a).

  • Chung, K. M., Lee, K. C., Choi, S. S., and Suh, H. W., Differential roles of spinal cholera toxin-and pertussis toxin sensitive G proteins in nociceptive responses caused by formalin, capsaicin and substance P in mice.Brain Res. Bull., 54, 537 (2001b).

    Article  PubMed  CAS  Google Scholar 

  • Clavelou, P., Callel, R., Orliaguet, T., Woda, A., and Raboisson, P., The orofacial formalin test in rats: effects of different formalin concentrations.Pain, 62, 295 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Cumberbatch, M., Herrero, J., and Headley, P., Exposure of rat spinal neurones to NMDA, AMPA and kainate produces only short-term enhancements of responses to noxious and non-noxious stimuli.Neurosci. Lett., 181, 98 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Damaj, M. I., Fei-Yin, M., Dukat, M., Glassco, W., Glennon, R. A., and Martin, B. R., Antinociceptive responses to nicotinic acetylcholine receptor ligands after systemic and intrathecal administration in mice.J. Pharmacol. Exp. Ther., 284, 1058 (1998).

    PubMed  CAS  Google Scholar 

  • DeLeo, J., Colburn, R., and Rickman, A., Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropethy.Brain Res., 759, 50 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Falchi, M., Ferrara, F., Gharib, C., and Dib, B., Hyperalgesic effect of intrathecally administered interleukin-1 in rats.Drugs Exp. Clin. Res., 27, 97 (2001).

    PubMed  CAS  Google Scholar 

  • Ferreira, J., Santos, A., and Calixto, J., The role of systemic, spinal and supraspinal L-arginine-nitric oxide-cGMP pathway in thermal hyperalgesia caused by intrathecal injection of glutamate in mice.Neuropharmacology, 38, 835 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Gamae, R. and Saria, A., Nociceptive behavior after intrathecal injections of substance P, neurokinin A and calcitonin gene-related peptide in mice.Neurosci. Lett., 70, 143 (1986).

    Article  Google Scholar 

  • Haley, T. J. M. W., Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse.Br. J. Pharmacol., 12, 12 (1957).

    CAS  Google Scholar 

  • Hopkins, S. J. and Rothwell, N. J., Cytokines and the nervous system: I. Expression and recognition.Trends Neurosci., 18, 83 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Hunskaar, S., Fasmer, O., and Fasmer, H. K., Formalin test in mice, a useful technique for evaluating mild analgesics.J. Neurosci. Methods, 14, 69 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Hunskaar, S. and Hunskaar, H. K., The formalin test in mice: dissociation between inflammatory and non-inflammatory pain.Pain, 30, 103 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Hunskaar, S., Post, C., Fasmer, O., and Arwestrom, E., Intrathecal injection of capsaicin can be used as a behavioural nociceptive test in mice.Neuropharmacology, 25, 1149 (1986).

    Article  PubMed  CAS  Google Scholar 

  • Hylden JI, W. G., Intrathecal morphine in mice: a new technique.Euro J. Psychopharmacology, 67, 313 (1980).

    Article  CAS  Google Scholar 

  • Hylden JI, W. G., Intrathecal substance P elicits a caudally-directed biting and scratching behavior in mice.Brain Res., 217 (1981).

  • Kidd, B. L. and Urban, L. A., Mechanisms of inflammatory pain.Br. J. Anaesth, 87, 3 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Koster, R., Anderson, M., and Beer, E. J., Acetic acid for analgesic screening.Federal proceeding, 18, 412 (1959).

    Google Scholar 

  • Maleki, N., Garjani, A., Nazemiyeh, H., Nilfouroushan, N., Sadat, A. E., Allameh, Z., and Hasannia, N., Potent anti-inflammatory activities of hydroalcoholic extract from aerial parts of Stachys inflata on rats.J. Ethnopharmacol., 75, 213 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Mattila, M. J., Ahtee, L., and Saarnivaara, L., The analgesic and sedative effects of nicotine in white mice, rabbits and golden hamsters.Ann. Med. Exp. Biol. Fenn., 46, 78 (1968).

    PubMed  CAS  Google Scholar 

  • Perkins, K. A., DiMarco, A., Grobe, J. E., Scierka, A., and Stiller, R. L., Nicotine discrimination in male and female smokers.Psychopharmacology (Berl), 116, 407 (1994).

    Article  CAS  Google Scholar 

  • Phan, D. V., Doda, M., Bite, A., and Gyorgy, L., Antin ociceptive activity of nicotine.Acta. Physiol. Acad. Sci. Hung., 44, 85 (1973).

    PubMed  CAS  Google Scholar 

  • Puig, S. and Sorkin, L. S., Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity.Pain, 64, 345 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Rashid, M. and Ueda, H., Neuropathy-specific analgesic action of intrathecal nicotinic agonists and its spinal GABA-mediated mechanism.Brain Res., 953, 53 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Rau, H., Schweizer, R., Zhuang, P., Pauli, P., Brody, S., Larbig, W., Heinle, H., Muller, M., Elbert, T., and Dworkin, B., Cigarette smoking, blood lipids, and baroreceptor-modulated nociception.Psychopharmacology (Berl), 110, 337 (1993).

    Article  CAS  Google Scholar 

  • Reeve, A. J., Patel, S., Fox, A., Walker, K., and Urban, L., Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat.Eur. J. Pain, 4, 247 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Riedel, W. and Neeck, G., Nociception, pain, and antinoci-ception: current concepts.Z. Rheumatol., 163, 404 (2001).

    Article  Google Scholar 

  • Schafers, M., Geis, C., Brors, D., Yaksh, T., and Sommer, C., Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve.J. Neurosci., 22, 536 (2002).

    PubMed  Google Scholar 

  • Shibata, M., Ohkubo, T., Takahashi, H., and Inoki, R., Modified formalin test: characteristic biphasic pain response.Pain, 38, 347 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Sommer, C., Lindenlaub, T., Teuteberg, P., Schafers, M., Hartung, T., and Toyka, K., Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy.Brain Res., 913, 86 (2001b).

    Article  PubMed  CAS  Google Scholar 

  • Sommer, C., Schafers, M., Marziniak, M., and Toyka, K., Etanercept reduces hyperalgesia in experimental painful neuropathy.J. Peripher. Nerv. Syst., 6, 67 (2001a).

    Article  PubMed  CAS  Google Scholar 

  • Vyklicky, L., Bonica, J. J., Liebeskind, J. C., and Albe-Fessard, D. G., Advances in pain Research and Therapy.Adv. Pain Res. The., 3, 727 (1979).

    Google Scholar 

  • Wagner, R., Myers, R., and O’Brien, J., Prosaptide prevents hyperalgesia and reduces peripheral TNFR! expression following TNF-alpha nerve injection.Neuroreport, 9, 2827 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Xu, X. J. H., J. Olsson, T. Kristensson, K. Van Der Meide, P. H. Meide, and Wiesenfeld Hallin H. Z., Intrathecal interferon-gamma facilitates the spinal nociceptive flexor reflex in the rat.Neurosci. Lett., 182, 263 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Zarrindast, M., Potentiation of imiprmine-induced antinoci-ception by nicotine in the formalin test.European Neuropsychopharmacology, 14, 71 (2003).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hong-Won Suh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Han, KJ., Choi, SS., Lee, JY. et al. Antinociceptive effect of nicotine in various pain models in the mouse. Arch Pharm Res 28, 209–215 (2005). https://doi.org/10.1007/BF02977717

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02977717

Key words

Navigation