Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-24T08:08:27.005Z Has data issue: false hasContentIssue false
  • English
  • Français

Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction injury rat model

Published online by Cambridge University Press:  30 June 2005

K. Okuda ,
T. Takanishi ,
K. Yoshimoto  and
S. Ueda
K. Okuda
Affiliation:
Dokkyo University School of Medicine, Department of Anaesthesiology, Mibu, Tochigi, Japan Dokkyo University School of Medicine, Department of Histology and Neurobiology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan
T. Takanishi
Affiliation:
Dokkyo University School of Medicine, Department of Anaesthesiology, Mibu, Tochigi, Japan
K. Yoshimoto
Affiliation:
Kyoto Prefectural University of Medicine, Department of Legal Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, Japan
S. Ueda
Affiliation:
Dokkyo University School of Medicine, Department of Histology and Neurobiology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan
Get access

Extract

Summary

Background and objective: Trazodone hydrochloride is used in the treatment of neuropathic pain. However, the analgesic effects of trazodone on neuropathic pain are controversial. The study was undertaken to determine the analgesic effect of trazodone on a chronic constriction injury model.

Methods: We tested the effect of trazodone on thermal hyperalgesia due to a chronic constriction injury of the sciatic nerve in rats and examined the effects of lesions in the descending and ascending serotonergic system induced by 5,7-dihydroxytriptamine (5,7-DHT).

Results: The analgesic effects of trazodone showed a clear dose dependency. Furthermore, the analgesic effect of trazodone was observed in rats injected with 5,7-DHT into the dorsal raphe nucleus and medial raphe nucleus.

Conclusions: The results suggest that a mainly serotonergic descending pain control pathway mediates the analgesic effects of trazodone.

Keywords

ANTIDEPRESSIVE AGENTS, SECOND-GENERATION, trazodoneINVESTIGATIVE TECHNIQUES, models, animalNERVOUS SYSTEM PHYSIOLOGY, SENSATION, painSOMATOSENSORY DISORDERS, hyperalgesia
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 5 , May 2003 , pp. 409 - 415
Copyright
2003 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Johnson BW, Parris WCV. Mechanisms of neuropathic pain. In: Raj PP, ed. Current Review of Pain.Philadelphia, USA: Current Medicine, 1994: 179–194.
Gershon S, Newton R. Lack of anticholinergic side effects with a new antidepressant – trazodone. J Clin Psychiat 1980; 41: 100–104.Google Scholar
Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Goodman Gilman A, Goodman L, Rall TW, Murad F, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics.New York, USA: Macmillan, 1985: 387–445.
Feighner JP. Trazodone, a triazolopyridine derivative, in primary depressive disorder. J Clin Psychiat 1980; 41: 250–255.Google Scholar
Feighner JP, Boyer WF. Overview of USA controlled trials of trazodone in clinical depression. Psychopharmacology 1988; 95: S50–S53.Google Scholar
Valeri P, Pimpinella G, Morrone LA, Romanelli L. Antinociceptive effects of trazodone and m-chlorophenylpiperazine (mCPP) in mice: interaction with morphine. Gen Pharmacol 1991; 22: 127–131.Google Scholar
Wilson RC. The use of low-dose trazodone in the treatment of painful diabetic neuropathy. J Am Podiat Med Assn 1999, 89: 468–471.Google Scholar
Ventafridda V, Caraceni A, Saita L, et al. Trazodone for deafferentation pain. Comparison with amitriptyline. Psychopharmacology 1988; 95: S44–S49.Google Scholar
Bennett GJ. An animal model of neuropathic pain: a review. Muscle Nerve 1993; 16: 1040–1048.Google Scholar
Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109–110.
Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87–107.Google Scholar
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates.New York, USA: Academic Press, 1996.
Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988; 32: 77–88.Google Scholar
Attal N, Jazat F, Kayser V, Guilbaud G. Further evidence for ‘pain-related’ behaviours in a model of unilateral peripheral mononeuropathy. Pain 1990; 41: 235–251.Google Scholar
Yamamoto T, Shimoyama N. Role of nitric oxide in the development of thermal hyperesthesia induced by sciatic nerve constriction injury in the rat. Anesthesiology 1995; 82: 1267–1273.Google Scholar
Basbaum AI, Fields HL. Endogenous pain control mechanisms: review and hypothesis. Ann Neurol 1978; 4: 451–462.Google Scholar
Tal M, Eliav E. Abnormal discharge originates at the site of nerve injury in experimental constriction neuropathy (CCI) in the rat. Pain 1996; 64: 511–518.Google Scholar
Carlton SM, Dougherty PM, Pover CM, Coggeshall RE. Neuroma formation and numbers of axons in a rat model of experimental peripheral neuropathy. Neurosci Lett 1991; 131: 88–92.Google Scholar
Munger BL, Bennett GJ, Kajander KC. An experimental painful peripheral neuropathy due to nerve constriction. I. Axonal pathology in the sciatic nerve. Exp Neurol 1992; 118: 204–214.Google Scholar
Nuytten D, Kupers R, Lammens M, Dom R, Van Hees J, Gybels J. Further evidence for myelinated as well as unmyelinated fibre damage in a rat model of neuropathic pain. Exp Brain Res 1992: 91: 73–78.Google Scholar
Basbaum AI, Gautron M, Jazat F, Mayes M, Guilbaud G. The spectrum of fiber loss in a model of neuropathic pain in the rat: an electron microscopic study. Pain 1991; 47: 359–367.Google Scholar
Ardid D, Guilbaud G. Antinociceptive effects of acute and ‘chronic’ injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats. Pain 1992; 49: 279–287.Google Scholar
Eschalier A. Antidepressants and pain management. In: Besson JM, ed. Serotonin and Pain.New York, USA: Elsevier, 1990: 305–326.
Haskins JT, Moyer JA, Muth EA, Sigg EB. DMI, Wy-45,030, Wy-45,881 and ciramadol inhibit locus coeruleus neuronal activity. Eur J Pharmacol 1985; 115: 139–146.Google Scholar
Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB. Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative. Biochem Pharmacol 1986; 35: 4493–4497.Google Scholar
Lang E, Hord AH, Denson D. Venlafaxine hydrochloride (Effexor™) relieves thermal hyperalgesia in rats with an experimental mononeuropathy. Pain 1996; 68: 151–155.Google Scholar
Willis WD, Westlund KN. Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 1997; 14: 2–31.Google Scholar
Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Ann Rev Neurosci 1984; 7: 309–338.Google Scholar
Besson JM, Chaouch A. Peripheral and spinal mechanisms of nociception. Physiol Rev 1987; 67: 67–186.Google Scholar
Fields HL, Basbaum AI, Clanton CH, Anderson SD. Nucleus raphe magnus inhibition of spinal cord dorsal horn neurons. Brain Res 1977; 126: 411–453.Google Scholar
Andersen E, Dafny N. Microiontophoretically applied 5-HT reduces responses to noxious stimuli in the thalamus. Brain Res 1982; 241: 176–178.Google Scholar
Beitz AJ. The anatomy of ascending serotonergic pathways possibly involved in pain modulation. In: Besson JM, ed. Serotonin and Pain.New York, USA: Elsevier, 1990: 31–51.
Azmitia EC, Segal M. An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J Comp Neurol 1978; 179: 641–659.Google Scholar
Andersen E, Dafny N. An ascending serotonergic pain modulation pathway from the dorsal raphe nucleus to the parafascicularis nucleus of the thalamus. Brain Res 1983; 269: 57–67.Google Scholar
Bowker RM, Westlund KN, Coulter JD. Origins of serotonergic projections to the spinal cord in rat: an immunocytochemical-retrograde transport study. Brain Res 1981; 226: 187–199.Google Scholar
Gebhart GF, Jones SL. Effects of morphine given in the brain stem on the activity of dorsal horn nociceptive neurons. Prog Brain Res 1988; 77: 229–243.Google Scholar
Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev 1992; 72: 165–229.Google Scholar
Fuller RW, Snoddy HD, Cohen ML. Interactions of trazodone with serotonin neurons and receptors. Neuropharmacology 1984; 23: 539–544.Google Scholar
Pazzagli M, Giovannini MG, Pepeu G. Trazodone increases extracellular serotonin levels in the frontal cortex of rats. Eur J Pharmacol 1999; 383: 249–257.Google Scholar
Eaton MJ, Santiago DI, Dancausse HA, Whittemore SR. Lumbar transplants of immortalized serotonergic neurons alleviate chronic neuropathic pain. Pain 1997; 72: 59–69.Google Scholar
Wang YX, Bowersox SS, Pettus M, Gao D. Antinociceptive properties of fenfluramine, a serotonin reuptake inhibitor, in a rat model of neuropathy. J Pharmacol Exp Ther 1999; 291: 1008–1016.Google Scholar
Barber A, Harting J, Wolf HP. Antinociceptive effects of the 5-HT2 antagonist ritanserin in rats: evidence for an activation of descending monoaminergic pathway in the spinal cord. Neurosci Lett 1989; 99: 234–238.Google Scholar
Bardin L, Lavarenne J, Eschalier A. Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats. Pain 2000; 86: 11–18.Google Scholar
Jackson WK, Roose SP, Glassman AH. Cardiovascular toxicity of antidepressant medications. Psychopathology 1987; 20 (Suppl 1): 64–74.Google Scholar