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Decreased basal endogenous opioid levels in diabetic rodents: effects on morphine and delta-9-tetrahydrocannabinoid-induced antinociception.
Eur J Pharmacol. 2008 Apr 14; 584(1):78-86.EJ

Abstract

We have previously demonstrated synergy between morphine and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in the expression of antinociception in acute pain models and in arthritic models of chronic pain. Our data has been extended to include acute pain in both diabetic mice and rats. In diabetic mice, Delta(9)-THC p.o. was more active in the tail-flick test in the diabetic mouse than in the non-diabetic mouse. Morphine (s.c.) was less potent in diabetic than in non-diabetic mice [6.1 (5.1-7.2) versus 3.2 (2.4-4.1) mg/kg, respectively], an effect previously extensively documented in pre-clinical and clinical testing. In addition, the combination of Delta(9)-THC with morphine produced a greater-than-additive relief of acute pain in mice. In the rat, the induction of the diabetic state decreased the antinociceptive effect of morphine, an effect temporally related to a decreased release of specific endogenous opioids. Conversely, Delta(9)-THC retained the ability to release endogenous opioids in diabetic rats and maintained significant antinociception. Extrapolation of such studies to the clinical setting may indicate the potential for use of Delta(9)-THC-like drugs in the treatment of diabetic neuropathic pain, alone or in combination with very low doses of opioids.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0524, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18313663

Citation

Williams, Jovan, et al. "Decreased Basal Endogenous Opioid Levels in Diabetic Rodents: Effects On Morphine and Delta-9-tetrahydrocannabinoid-induced Antinociception." European Journal of Pharmacology, vol. 584, no. 1, 2008, pp. 78-86.
Williams J, Haller VL, Stevens DL, et al. Decreased basal endogenous opioid levels in diabetic rodents: effects on morphine and delta-9-tetrahydrocannabinoid-induced antinociception. Eur J Pharmacol. 2008;584(1):78-86.
Williams, J., Haller, V. L., Stevens, D. L., & Welch, S. P. (2008). Decreased basal endogenous opioid levels in diabetic rodents: effects on morphine and delta-9-tetrahydrocannabinoid-induced antinociception. European Journal of Pharmacology, 584(1), 78-86. https://doi.org/10.1016/j.ejphar.2007.12.035
Williams J, et al. Decreased Basal Endogenous Opioid Levels in Diabetic Rodents: Effects On Morphine and Delta-9-tetrahydrocannabinoid-induced Antinociception. Eur J Pharmacol. 2008 Apr 14;584(1):78-86. PubMed PMID: 18313663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decreased basal endogenous opioid levels in diabetic rodents: effects on morphine and delta-9-tetrahydrocannabinoid-induced antinociception. AU - Williams,Jovan, AU - Haller,Victoria L, AU - Stevens,David L, AU - Welch,Sandra P, Y1 - 2008/02/05/ PY - 2007/09/05/received PY - 2007/12/11/revised PY - 2007/12/20/accepted PY - 2008/3/4/pubmed PY - 2008/7/11/medline PY - 2008/3/4/entrez SP - 78 EP - 86 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 584 IS - 1 N2 - We have previously demonstrated synergy between morphine and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in the expression of antinociception in acute pain models and in arthritic models of chronic pain. Our data has been extended to include acute pain in both diabetic mice and rats. In diabetic mice, Delta(9)-THC p.o. was more active in the tail-flick test in the diabetic mouse than in the non-diabetic mouse. Morphine (s.c.) was less potent in diabetic than in non-diabetic mice [6.1 (5.1-7.2) versus 3.2 (2.4-4.1) mg/kg, respectively], an effect previously extensively documented in pre-clinical and clinical testing. In addition, the combination of Delta(9)-THC with morphine produced a greater-than-additive relief of acute pain in mice. In the rat, the induction of the diabetic state decreased the antinociceptive effect of morphine, an effect temporally related to a decreased release of specific endogenous opioids. Conversely, Delta(9)-THC retained the ability to release endogenous opioids in diabetic rats and maintained significant antinociception. Extrapolation of such studies to the clinical setting may indicate the potential for use of Delta(9)-THC-like drugs in the treatment of diabetic neuropathic pain, alone or in combination with very low doses of opioids. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18313663/Decreased_basal_endogenous_opioid_levels_in_diabetic_rodents:_effects_on_morphine_and_delta_9_tetrahydrocannabinoid_induced_antinociception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00100-3 DB - PRIME DP - Unbound Medicine ER -