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Central beta-endorphin system involvement in the reaction to acute tonic pain

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Summary

The involvement of the beta-endorphin (B-EP) system during acute prolonged (tonic) pain was investigated by biochemical and behavioral approaches in freely-moving rats after subcutaneous injection of a small amount of a dilute formaldehyde solution (0.08 ml, 5%) in a forepaw. Beta-endorphin-like immunoreactivity levels were increased over the respective control groups in rats killed 30, 60 and 120 min after injection in discrete regions of the rat brain, namely ventro-medial hypothalamus, ventro-basal thalamus and periaqueductal gray matter, and at 30 and 60 min in postero-medial thalamus. In a separate group of experiments a small amount of anti-B-EP or normal rabbit serum was injected in the lateral ventricle; 6 h later rats received formalin injection as in previous groups and their behavior was scored over the following 2 h. A significant hyperalgesia (as expressed by an increase in the amount of time rats spent licking or chewing the injected paw) was observed 10–50 min and 70–80 min after formalin in the anti-B-EP icv-injected group. Other behavioral parameters such as general motor activity, grooming and limb flexion were not different in the two groups, nor was animal behavior prior to formalin injection. Altogether these data suggest that the central beta-endorphin system is triggered by prolonged noxious stimulation in freely-moving animals, and in turn plays a physiological role in the modulation of the reaction to, or perception of, tonic pain.

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References

  • Abbott FV, Melzack R (1983) Dissociation of the mechanisms of stimulation-produced analgesia in test of tonic and phasic pain. In: Bonica JJ et al. (eds) Advances in pain research and therapy, Vol. 5. Raven, New York, pp 401–409

    Google Scholar 

  • Abbott FV, Melzack R, Samuel C (1982) Morphine analgesia in the tail-flick and formalin pain tests is mediated by different neural systems. Exp Neurol 75:644–651

    Google Scholar 

  • Albe-Fessard D, Berkley KJ, Kruger L, Ralston HJ, Willis WD (1985) Diencephalic mechanisms of pain sensation. Brain Res Rev 9:217–296

    Google Scholar 

  • Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Ann Rev Neurosci 7:309–38

    Google Scholar 

  • Carli G, Farabollini F, Fontani G (1981) Effects of pain, morphine and naloxone on the duration of animal hypnosis. Behav Brain Res 2:373–385

    Google Scholar 

  • Carr KD, Bak TH (1988) Medial thalamic injection of opioid agonists: mu-agonist increases while k-agonist decreases stimulus thresholds for pain and reward. Brain Res 441:173–184

    Google Scholar 

  • Cohen SR, Melzack R (1985) Morphine injected into the habenula and dorsal posteromedial thalamus produces analgesia in the formalin test. Brain Res 359:131–139

    Google Scholar 

  • Cohen SR, Melzack R (1986) Habenular stimulation produces analgesia in the formalin test. Neurosci Lett 70:165–169

    Google Scholar 

  • Dickenson AH, Sullivan AF (1987) Subcutaneous formalin-induced activity of dorsal horn neurones in the rat: differential response to an intrathecal opiate administered pre or post formalin. Pain 30:349–360

    Google Scholar 

  • Dubuisson D, Dennis SG (1977) The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4:161–174

    Google Scholar 

  • Fanselow MS (1984) Shock-induced analgesia on the formalin test: effects of shock severity, naloxone, hypophysectomy, and associative variables. Behav Neurosci 98:79–95

    Google Scholar 

  • Fields HL, Basbaum AI (1989) Endogenous pain control mechanisms. In: Wall PD, Melzack R (eds) Textbook of pain, 2nd edn. Churchill Livingstone, Edinburgh, pp 206–219

    Google Scholar 

  • Finley JCW, Lindstrom P, Petrusz P (1981) Immunocytochemical localization of beta-endorphin-containing neurons in the rat brain. Neuroendocrinol 33:28–42

    Google Scholar 

  • Guilbaud G, Peschanski M, Besson J-M (1989) Experimental data related to nociception and pain at the supraspinal level. In: Wall PD, Melzack R (eds) Textbook of pain, 2nd edn. Churchill Livingstone, Edinburgh, pp 141–153

    Google Scholar 

  • Hamba M (1988) Effects of lesion and stimulation of rat hypothalamic arcuate nucleus on the pain system. Brain Res Bull 21:757–763

    Google Scholar 

  • Herkenham M (1987) Mismatches between neurotransmitter and receptor localization in brain: observations and implications. Neurosci 23:1–38

    Google Scholar 

  • Herz A, Millan MJ (1988) Endogenous opioid peptides in the descending control of nociceptive responses of spinal dorsal horn neurons. Progr Brain Res 77:263–274

    Google Scholar 

  • Kayser V, Besson J-M, Guilbaud G (1988) Paradoxical effects of low doses of naloxone in experimental models of inflammatory pain. Progr Brain Res 77:301–312

    Google Scholar 

  • Klemm F, Carli G, Reeh PW (1989) Peripheral neural correlates of the formalin test in the rat. Eur J Physiol 414:S42

    Google Scholar 

  • Kocher L (1988) Systemic naloxone does not affect pain-related behaviour in the formalin test in rat. Physiol Behav 43:265–268

    Google Scholar 

  • Kuraishi Y, Sugimoto M, Hamada T, Kayanoki Y, Takagi H (1984) Noxious stimuli and met-enkephalin release from nucleus reticularis gigantocellularis. Brain Res Bull 12:123–127

    Google Scholar 

  • Millan MJ (1986) Multiple opioid systems and pain. Pain 27:303–347

    Google Scholar 

  • Nayar U (1989) Mechanisms modulating tonic pain in monkeys. In: Proc XXXI International Congress of Physiological Sciences, p S1052

  • North MA (1978) Naloxone reversal of morphine analgesia but failure to alter reactivity to pain in the formalin test. Life Sci 22:295–302

    Google Scholar 

  • Ogawa N, Panerai AE, Lee S, Forsbach S, Havlicek H, Friesen HG (1979) Beta-endorphin concentration in brain of intact and hypophysectomized rats. Life Sci 25:317–326

    Google Scholar 

  • Palkovits M (1973) Isolated removal of hypothalamic and other brain nuclei of the rat. Brain Res 59:449–450

    Article  CAS  PubMed  Google Scholar 

  • Panerai AE, Martini A, Sacerdote P, Mantegazza P (1984) K-receptor antagonist reverses “non-opioid” stress-induced analgesia. Brain Res 304:153–156

    Google Scholar 

  • Panerai AE, Sacerdote P, Brini A, Mantegazza P (1987) Analgesic effect of morphine: a role for beta-endorphin. Neurosci Lett 74:348–352

    Google Scholar 

  • Paxinos G, Watson G (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, Sydney

    Google Scholar 

  • Porro CA, Facchinetti F, Pozzo P, Benassi C, Biral GP, Genazzani AR (1988) Tonic pain time-dependently affects beta-endorphin-like immunoreactivity in the ventral periaqueductal gray matter of the rat brain. Neurosci Lett 86:89–93

    Google Scholar 

  • Reichling DB, Kwiat GC, Basbaum AI (1988) Anatomy, physiology and pharmacology of the periaqueductal gray — contribution to antinociceptive controls. Progr Brain Res 77:31–46

    Google Scholar 

  • Ryan SM, Watkins LR, Mayer DJ, Maier SF (1985) Spinal pain suppression mechanisms may differ for phasic and tonic pain. Brain Res 334:172–175

    Google Scholar 

  • Sugimoto M, Kuraishi Y, Satoh M, Takagi H (1986) Involvement of medullary opioid-peptidergic and spinal noradrenergic systems in the regulation of formalin-induced persistent pain. Neuropharmacol 25:481–485

    Google Scholar 

  • Tasker RAR, Choiniere M, Libman SM, Melzack R (1987) Analgesia produced by injection of lidocaine into the lateral hypothalamus. Pain 31:237–248

    Google Scholar 

  • Terman GW, Shavit Y, Lewis JW, Cannon JT, Liebeskind JC (1984) Intrinsic mechanisms of pain inhibition: activation by stress. Science 226:1270–1277

    Google Scholar 

  • Vaccarino AL, Melzack R (1989) Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain 39:213–220

    Google Scholar 

  • Vaccarino AL, Tasker RA, Melzack R (1989) Analgesia produced by normal doses of opioid antagonists alone and in combination with morphine. Pain 36:103–109

    Google Scholar 

  • Watkins LR, Mayer DJ (1982) Organization of opiates and non-opiates pain control systems. Science 216:1185–1192

    Google Scholar 

  • Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109–110

    Google Scholar 

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Porro, C.A., Tassinari, G., Facchinetti, F. et al. Central beta-endorphin system involvement in the reaction to acute tonic pain. Exp Brain Res 83, 549–554 (1991). https://doi.org/10.1007/BF00229833

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