Email this article The possible mechanisms of analgesia produced by microinjection of morphine into the lateral habenula in the acute model of trigeminal pain in rats
Abstract
This study aimed to assess the effect of intra-habenular injection of morphine on acute trigeminal pain in rats. Also here, we examined the involvement of raphe nucleus opioid and 5HT3 receptors on the antinociceptive activity of intra habenular morphine to explore the possibility of existence of descending antinociceptive relay between the habenula and raphe nucleus. The numbers of eye wiping response elicited by applying a drop (40 µL) of NaCl (5 M) solution on the corneal surface were taken as an index of acute trigeminal nociception. Intra habenular microinjection of morphine at a dose of 2 μg was without effect, whereas at doses of 5 and 8 μg significantly produced antinociception. Microinjection of naltrexone (4 µg) and ondansetron (1 µg) into the dorsal raphe nucleus prior to intra-habenular saline did not produce any significant effect on corneal pain perception. Pretreatment of the raphe nucleus with ondansetron but not naltrexone prevented intra habenular morphine (8 μg) induced antinociception. Also, intra habenular injection of lidocaine (2%, 0.5 µL) reduced corneal pain response. Moreover, intra-habenular microinjection of L-glutamic acid (1 and 2 µg/site) did not produce any analgesic activity in this model of pain. In conclusion, the present results suggest that the activation of the habenular µ opioid receptor by microinjection of morphine or inhibition of habenular neurons by microinjection of lidocaine produced an analgesic effect in the acute trigeminal model of pain in rats. The analgesic effect of intra habenular morphine was blocked by intra-dorsal raphe injection of serotonin 5-HT3 antagonist.
Keywords
Full Text:
PDFReferences
Amat J, Sparks PD, Matus-Amat P, Griggs J, Watkins LR, Maier SF. The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress. Brain Res. 2001;917(1):118-126.
Hikosaka O. The habenula: from stress evasion to value-based decisionmaking. Nat Rev Neurosci. 2010;11(7):503-513.
Dafny N, Dong WQ, Prieto-Gomez C, Reyes-Vazquez C, Stanford J, Qiao JT. Lateral hypothalamus: site involved in pain modulation. Neuroscience. 1996;70:(2)449-460.
Shelton L, Becerra L, Borsook D. Unmasking the mysteries of the habenula in pain and analgesia. Prog Neurobiol. 2012;96(2):208-219.
Cohen SR, Melzack R. Habenular stimulation produces analgesia in the formalin test. Neurosci Lett. 1986;70(1):165-169.
Cohen SR, Melzack R. Morphine injected into the habenula and dorsal posteromedial thalamus produces analgesia in the formalin test. Brain Res. 1985;359(1-2):131-139.
Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ. Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. J Neurosci. 1987;7(8):2445-2464.
Hashimoto K, Amano T, Sakai N, Suzuki T, Narita M. Cell-dependent physiological synaptic action of morphine in the rat habenular nucleus: morphine both inhibits and facilitates excitatory synaptic transmission. Neurosci Lett. 2009;451(3):270-273.
Gao DM, Hoffman D, Benabid AL. Simultaneous recording of spontaneous activities and nociceptive responses from neurons in the pars compacta of substantia nigra and in the lateral habenula. Eur J Neurosci. 1996;8(7):1474-1478.
Goto M, Canteras NS, Burns G, Swanson LW. Projections from the subfornical region of the lateral hypothalamic area. J Comp Neurol. 2005;493(3):412-438.
Craig AD. Distribution of trigeminothalamic and spinothalamic lamina I terminations in the cat. Somatosens Mot Res. 2003;20(3-4):209-222.
Ferraro G, Montalbano ME, Sardo P, La Grutta V. Lateral habenular influence on dorsal raphe neurons. Brain Res Bull. 1996;41(1):47-52.
Alenina N, Bashammakh S, Bader M. Specification and differentiation of serotonergic neurons. Stem Cell Rev. 2006;2(1):5-10.
Bianco IH, Wilson SW. The habenular nuclei: a conserved asymmetric relay station in the vertebrate brain. Philos Trans R Soc Lond B Biol Sci. 2009;364(1519):1005-1020.
Wang QP, Nakai Y. The dorsal raphe: an important nucleus in pain modulation. Brain Res Bull. 1994;34(6):575-585.
Beitz AJ, Clements JR, Ecklund LJ, Mullett MM. The nuclei of origin of brainstem enkephalin and cholecystokinin projections to the spinal trigeminal nucleus of the rat. Neuroscience. 1987;20(2):409-425.
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983;16(2):109-110.
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed., New York, USA, Elsevier, 2007. p. 61-110.
Erfanparast A, Tamaddonfard E, Farshid AA, Khalilzadeh E. Antinociceptive effect of morphine microinjections into the dorsal hippocampus in the formalin-induced orofacial pain in rats. Veterinary Research Forum. 2010;1:83-89.
Haghparast A, Ahmad-Molaei L, Alizadeh A, Azizi P. Blockade of opioid receptors located in the rat nucleus cuneiformis reduced the antinociceptive responses of local but not systemic administration of morphine in formalin test. Basic and Clinical Nurosciense. 2010;2:13-19.
Miranda MI, Ferreira G, Ramírez-Lugo L, Bermúdez-Rattoni F. Glutamatergic activity in the amygdala signals visceral input during taste memory formation. Proc Natl Acad Sci USA. 2002;99(17):11417-11422.
Helmstetter FJ, Landeira-Fernandez J. Conditional hypoalgesia is attenuated by Naltrexone applied to the periaqueductal gray. Brain Res. 1999;537(1-2):88–92.
Ohmura Y, Yoshida T, Konno K, Minami M, Watanabe M, Yoshioka M. Serotonin 5-HT7 receptor in the ventral hippocampus modulates the retrieval of fear memory and stress-induced defecation. Int J Neuropsychopharmacol. 2015;19(6):1-12.
Farazifard R, Safapour F, Sheibani V, Javan M. Eye wiping test: a sensitive animal model for acute trigeminal pain studies. Brain Res Brain Res Protoc. 2005;16(1-3):44-49.
Khalilzadeh E, Hazrati R, Vafaei Saiah G. Effects of topical and systemic administration of Eugenia caryophyllata buds essential oil on corneal anesthesia and analgesia. Res Pharm Sci. 2016;11(4):293-302.
Lehner M, Taracha E, Skorzewska A, Wislowska A, Zienowicz M, Maciejak P, et al. Sensitivity to pain and c-Fos expression in brain structures in rats. Neurosci Lett. 2004;370(1):74-79.
Wang RY, Aghajanian GK. Physiological evidence for habenula as major link between forebrain and midbrain raphe. Science. 1977;197(4298):89-91.
Yang LM, Hu B, Xia YH, Zhang BL, Zhao H. Lateral habenula lesions improve the behavioral response in depressed rats via increasing the serotonin level in dorsal raphe nucleus. Behav Brain Res. 2008;188(1):84-90.
Kalen P, Strecker RE, Rosengren E, Bjorklund A. Regulation of striatal serotonin release by the lateral habenula–dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and GABA. Brain Res. 1989;492(1-2):187-202.
Waselus M, Galvez JP, Valentino RJ, Van Bockstaele EJ. Differential projections of dorsal raphe nucleus neurons to the lateral septum and striatum. J Chem Neuroanat. 2006;31(4):233-242.
Zhao H, Wang S. Different effects of l-glutamate microinjection into medial or lateral habenular nucleus on pain threshold. Sheng Li Xue Bao. 1995;47(3):292-296.
Cohen SR, Melzack R. The habenula and pain: repeated electrical stimulation produces prolonged analgesia but lesions have no effect on formalin pain or morphine analgesia. Behav Brain Res. 1993;54(2):171-178.
Ferraro G, Montalbano ME, Sardo P, La Grutta V. Lateral habenula and hippocampus: a complex interaction raphe cells mediated. J Neural Transm. 1997;104(6-7):615-631.
Nishikawa T, Scatton B. Inhibitory influence of GABA on central serotonergic transmission. Involvement of the habenulo-raphe pathways in the GABAergic inhibition of ascending cerebral serotonergic neurons. Brain Res. 1985;331:81-90.
Sabatino M, Ferraro G, La Grutta V. Relay stations and neurotransmitters between the palidal region and the hippocampus. Electroencephalogr Clin Neurophysiol. 1991;78(4):302-310.
Millan MJ. The role of descending noradrenergic and serotoninergic pathways in the modulation of nociception: focus on receptor multiplicity, Handbook of experimental pharmacology, Vol. 130. In: Dickenson AH, Besson JM, editors. The pharmacology of pain, Heidelberg: Springer. 1997;385-446.
Wigdor S, Wilcox GL. Central and systemic morphine-induced antinociception in mice: contribution of descending serotonergic and noradrenergic pathways. J Pharmacol Exp Ther. 1987;242(1):90-95.
Laporte AM, Koscielniak T, Ponchant M, Vergé D, Hamon M, Gozlan H. Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodo-zacopride and [3H]zacopride as radioligands. Synapse. 1992;10(4):271-281.
Glaum SR, Proudfit HK, Anderson EG. Reversal of the antinociceptive effects of intrathecally administered serotonin in the rat by a selective 5HT3 receptor antagonist. Neurosci Lett. 1988;95(1-3):313-317.
Glaum SR, Proudfit HK, Anderson EG. 5HT3 receptors modulate spinal nociceptive reflexes. Brain Res. 1990;510(1):12-16.
Bardin L, Jourdan D, Alloui A, Lavarenne J, Eschalier A. Differential influence of two serotonin 5-HT3 receptor antagonists on spinal serotonin-induced analgesia in rats. Brain Res. 1997;765(2):267-272.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.