Analgesia, morphine

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

An intriguing area of research on opioids has been the accumulating evidence for plasticity in opioid controls. The degree of effectiveness of morphine analgesia is snbject to modulation by other transmitter systems in the spinal cord and by pathological changes induced by peripheral nerve injury. Thus in neuropathic states, pain after nerve injury, morphine analgesia can be reduced (but can still be effective) and tactics other than dose-escalation to circumvent this will be briefly discussed in Chapter 21. 

Bohn L, Lefkowitz R et al. Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science 1999 286 2495-2498. 

Interactions are seen between cocaine and the opioid system in analgesia. A synergistic effect occurs when cocaine is combined with a ju agonist (morphine) in the hot-plate test and a k agonist (U69,593) in the hot-plate test (Waddell and Holtzman 1999). Cocaine enhances morphine analgesia in several analgesic paradigms (e.g., formalin test, hot-plate test, and thermal tail-flick test)... 

Malec D, Michalska E. (1988). The effect of methyixanthines on morphine analgesia in mice and rats. Pol J Pharmacol Pharm. 40(3) 223-32. 

Misra AL, Pontani RB, Vadlamani NL. (1985). Potentiation of morphine analgesia by caffeine. BrJ Pharmacol. 84(4) 789-91. 

Paul D, Mana MJ, Pfaus JG, Pinel JP. (1988). Attenuation of morphine analgesia by the S2 antagonists, pirenperone and ketanserin. Pharmacol Biochem Behav. 31(3) 641 7. 

Rossi G, Pan YX, Cheng J, Pasternak GW. (1994). Blockade of morphine analgesia by an antisense oligodeoxynucleotide against the mu receptor. Life Sci. 54 375-79. 

Rossi GC, Pasternak GW, Bodnar RJ. (1993). Synergistic brainstem interactions for morphine analgesia. Brain Res. 624 171-80. 

Spinella M, Bodnar RJ. (1996). Excitatory amino acid antagonists in the rostro-ventral medulla inhibit mesencephalic morphine analgesia in rats. Pain. 64 545-52. 

Spinella M, Schaeffer LA, Bodnar RJ. (1997). Ventral medullary mediation of mesencephalic morphine analgesia by muscarinic and nicotinic cholinergic receptor antagonists in rats. Analgesia. 3 119-30. 

Morphine Analgesia, miosis, respiratory depression, bradycardia, hypothermia, inattention to external stimuli p-receptor... 

Lipp, J. Possible mechanisms of morphine analgesia, Clin. Neuropharmacol. 1991, 14, 131-147. 

Borszcz, G. S. Differential contributions of medullary, thalamic, and amygdaloid serotonin to the antinociceptive action of morphine administered into the periaqueductal gray a model of morphine analgesia, Behav. Neurosci. 1999, 133, 612-631. 

Ikeda et al., 2000 Narita et al., 2000). KAtp channels have been shown to be opened by Gj/0-proteins (Edwards and Weston, 1993) and could thus mediate the inhibitory effect of morphine at the cellular level. Furthermore, such an interaction would also explain the antagonism and potentiation of morphine analgesia by Katp channel blockers and openers, respectively (see above). However, a recent electrophysiological study demonstrated that Katp channels do not mediate the effect of morphine in ventrolateral PAG neurones (Chiou and How, 2001). 

Davis, W. M., Miya, T. S., Edwards L. D. The influence of glucose and insulin pretreatment upon morphine analgesia in the rat, Journal of the American Pharmacological Association 1956, 45, 60-62. 

Ocana, M., Del Pozo, E., Barrios, M., Robles, L. I., Baeyens, J. M. An ATP-dependent potassium channel blocker antagonizes morphine analgesia, European Journal of Pharmacology 1990, 186, 377-378. 

Vergoni, A. V., Scarano, A., Bertolini, A. Pinacidil potentiates morphine analgesia, Life Sciences 1992, 50, 135-138. 

Basilico, L., Parolaro, D., Rubino, T., Gori, E., Giagnoni, G. Influence of co-conotoxin on morphine analgesia and withdrawal syndrome in rats, Eur. J. Pharmacol. 1992, 218, 75-81. 

Michaluk, J., Karolewicz, B., Antkiewicz-Michaluk, L., Ventulani, J. Effects of various Ca2 channel antagonists on morphine analgesia, tolerance and dependence, and on blood pressure in the rat, Eur. J. Pharmacol. 1998, 352, 189-197. 

Smith, F.L. and Stevens, D.L. Calcium modulation of morphine analgesia role of calcium channels and intracellular pool calcium, J. Pharmacol. Exp. Ther. 1995, 272, 290-299. 

Ueda, H., Yamaguchi, T., Tokuyama, S., Inoue, M., Nishi, M., Takeshima, H. Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene, Neuroscience Lett. 1997, 237, 136-138. 

Salmon, A.-M., Damaj, M.I., Sekine, S., Picciotto, M.R., Marubio, L., Changeux, J.-P. Modulation of morphine analgesia in aCGRP mutant mice, Neuroreport 1999, 10, 849-854. 

Somatostatin and its analogues have been reported to be OP3 ( i) opioid receptor antagonists (57). Somatostatin infusions significantly reduced the effectiveness of morphine analgesia in a case report of three patients with cancer. 

M.M. Antibodies to G ganglioside block morphine analgesia. Neurosci. Abstr., 1978, 4, 460. 

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