Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors

Molecular Pain

Masamichi Satoh¹  Masabumi Minami²  Hiroshi Satoyoshi²  Soichiro Ide³ 

[1] Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan;Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan;Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

关键词: Serotonin reuptake inhibitor;    Noradrenalin reuptake inhibitor;    Tramadol;    Morphine;    Analgesia;    Pain;    Unpredictable chronic mild stress;    Opioid;   

Others  :  1226132
DOI  :  10.1186/s12990-015-0051-0

 received in 2015-02-13, accepted in 2015-07-28,  发布年份 2015

【 摘 要 】

Background

Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of μ-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition.

Results

Unpredictable chronic mild stress did not affect the basal thermal pain sensitivity in a mouse hot-plate test. Although morphine dose-dependently induced thermal antinociceptive effects under both the UCMS and non-stress conditions, the thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly lower than under the non-stressed condition. Unlike the case with morphine, we observed no significant difference in the thermal antinociceptive effect of tramadol between the UCMS and non-stress conditions. Furthermore, the reduced thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly ameliorated by pretreatment with 10 mg/kg maprotiline but not 3 mg/kg escitalopram. Pretreatment with neither maprotiline nor escitalopram alone was associated with an antinociceptive effect under either condition.

Conclusions

We demonstrated that the antinociceptive effect of morphine but not tramadol was reduced in mice that had experienced UCMS. The reduced antinociceptive effect of morphine under the UCMS condition was ameliorated by pretreatment with maprotiline but not escitalopram. These results suggest that the reduced antinociceptive effects of morphine under conditions of chronic stress may be ameliorated by activation of the noradrenergic but not the serotonergic system.

【 授权许可】

   
2015 Ide et al.

【 图 表 】

Fig.1.

Fig.2.

Fig.3.

Fig.4.

【 参考文献 】

• [1]Appelbaum BD, Holtzman SG: Stress-induced changes in the analgesic and thermic effects of opioid peptides in the rat. Brain Res 1986, 377(2):330-336.
• [2]Calcagnetti DJ, Holtzman SG: Factors affecting restraint stress-induced potentiation of morphine analgesia. Brain Res 1990, 537(1–2):157-162.
• [3]Vanderah TW, Wild KD, Takemori AE, Sultana M, Portoghese PS, Bowen WD, et al.: Modulation of morphine antinociception by swim-stress in the mouse: involvement of supraspinal opioid δ-2 receptors. J Pharmacol Exp Ther 1993, 267(1):449-455.
• [4]da Silva Torres IL, Cucco SN, Bassani M, Duarte MS, Silveira PP, Vasconcellos AP, et al.: Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration. Neurosci Res 2003, 45(3):277-283.
• [5]Girardot MN, Holloway FA: Intermittent cold water stress-analgesia in rats: cross-tolerance to morphine. Pharmacol Biochem Behav 1984, 20(4):631-633.
• [6]Loh HH, Liu HC, Cavalli A, Yang W, Chen YF, Wei LN: μ Opioid receptor knockout in mice: effects on ligand-induced analgesia and morphine lethality. Brain Res Mol Brain Res 1998, 54(2):321-326.
• [7]Sora I, Takahashi N, Funada M, Ujike H, Revay RS, Donovan DM, et al.: Opiate receptor knockout mice define μ receptor roles in endogenous nociceptive responses and morphine-induced analgesia. Proc Natl Acad Sci USA 1997, 94(4):1544-1549.
• [8]Sora I, Elmer G, Funada M, Pieper J, Li XF, Hall FS, et al.: μ Opiate receptor gene dose effects on different morphine actions: evidence for differential in vivo μ receptor reserve. Neuropsychopharmacology 2001, 25(1):41-54.
• [9]Ide S, Minami M, Ishihara K, Uhl GR, Sora I, Ikeda K: μ Opioid receptor-dependent and independent components in effects of tramadol. Neuropharmacology 2006, 51(3):651-658.
• [10]Lee CR, McTavish D, Sorkin EM: Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993, 46(2):313-340.
• [11]Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL, et al.: Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther 1993, 267(1):331-340.
• [12]Driessen B, Reimann W: Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. Br J Pharmacol 1992, 105(1):147-151.
• [13]Driessen B, Reimann W, Giertz H: Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro. Br J Pharmacol 1993, 108(3):806-811.
• [14]Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL: Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992, 260(1):275-285.
• [15]Clark WC, Yang JC, Janal MN: Altered pain and visual sensitivity in humans: the effects of acute and chronic stress. Ann N Y Acad Sci 1986, 467:116-129.
• [16]Imbe H, Iwai-Liao Y, Senba E: Stress-induced hyperalgesia: animal models and putative mechanisms. Front Biosci 2006, 11:2179-2192.
• [17]Pinto-Ribeiro F, Almeida A, Pego JM, Cerqueira J, Sousa N: Chronic unpredictable stress inhibits nociception in male rats. Neurosci Lett 2004, 359(1–2):73-76.
• [18]Shi M, Qi WJ, Gao G, Wang JY, Luo F: Increased thermal and mechanical nociceptive thresholds in rats with depressive-like behaviors. Brain Res 2010, 1353:225-233.
• [19]Zomkowski AD, Engel D, Gabilan NH, Rodrigues AL: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. Eur Neuropsychopharmacol 2010, 20(11):793-801.
• [20]Chen P, Fan Y, Li Y, Sun Z, Bissette G, Zhu MY: Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains. Neurochem Int 2012, 60(1):9-20.
• [21]Bravo L, Torres-Sanchez S, Alba-Delgado C, Mico JA, Berrocoso E: Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats. Eur Neuropsychopharmacol 2014, 24(6):996-1003.
• [22]Alba-Delgado C, Llorca-Torralba M, Horrillo I, Ortega JE, Mico JA, Sanchez-Blazquez P, et al.: Chronic pain leads to concomitant noradrenergic impairment and mood disorders. Biol Psychiatry 2013, 73(1):54-62.
• [23]Mika J, Zychowska M, Makuch W, Rojewska E, Przewlocka B: Neuronal and immunological basis of action of antidepressants in chronic pain—clinical and experimental studies. Pharmacol Rep 2013, 65(6):1611-1621.
• [24]Woolfe G, MacDonald A: The evaluation of the analgesic action of pethidine hydrochloride (demerol). J Pharmacol Exp Ther 1944, 80:300-307.
• [25]Ide S, Minami M, Sora I, Ikeda K: Combination of cell culture assays and knockout mouse analyses for the study of opioid partial agonism. Methods Mol Biol 2010, 617:363-374.