Tags

Type your tag names separated by a space and hit enter

Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice.
Brain Behav Immun. 2009 Jan; 23(1):75-84.BB

Abstract

We have previously demonstrated that glial inhibitors reduce the development of allodynia and hyperalgesia, potentiating the effect of a single morphine dose in a neuropathic pain model. This study explores the effects of two glial activation inhibitors, minocycline and pentoxifylline, on the development of tolerance to morphine in naive and chronic constriction injury (CCI)-exposed mice. Administration of morphine to naive (20 mg/kg; i.p.) and CCI-exposed mice (40 mg/kg; i.p.) twice daily resulted in tolerance to its anti-nociceptive effect after 6 days. Injections of morphine were combined with minocycline (30 mg/kg, i.p.) or pentoxifylline (20 mg/kg, i.p.) administered as two preemptive doses before first morphine administration in naive or pre-injury in CCI-exposed mice, and repeated twice daily 30 min before each morphine administration. With treatment, development of morphine tolerance was delayed by 5 days (from 6 to 11 days), as measured by the tail-flick test in naive and by tail-flick, von Frey, and cold plate tests in CCI-exposed mice. Western blot analysis of CD11b/c and GFAP protein demonstrated that minocycline and pentoxifylline, at doses delaying development of tolerance to morphine analgesia, significantly diminished the morphine-induced increase in CD11b/c protein level. We found that repeated systemic administration of glial inhibitors significantly delays development of morphine tolerance by attenuating the level of this microglial marker under normal and neuropathic pain conditions. Our results support the idea that targeting microglial activation during morphine therapy/treatment is a novel and clinically promising method for enhancing morphine's analgesic effects, especially in neuropathic pain.

Authors+Show Affiliations

Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18684397

Citation

Mika, Joanna, et al. "Attenuation of Morphine Tolerance By Minocycline and Pentoxifylline in Naive and Neuropathic Mice." Brain, Behavior, and Immunity, vol. 23, no. 1, 2009, pp. 75-84.
Mika J, Wawrzczak-Bargiela A, Osikowicz M, et al. Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice. Brain Behav Immun. 2009;23(1):75-84.
Mika, J., Wawrzczak-Bargiela, A., Osikowicz, M., Makuch, W., & Przewlocka, B. (2009). Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice. Brain, Behavior, and Immunity, 23(1), 75-84. https://doi.org/10.1016/j.bbi.2008.07.005
Mika J, et al. Attenuation of Morphine Tolerance By Minocycline and Pentoxifylline in Naive and Neuropathic Mice. Brain Behav Immun. 2009;23(1):75-84. PubMed PMID: 18684397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice. AU - Mika,Joanna, AU - Wawrzczak-Bargiela,Agnieszka, AU - Osikowicz,Maria, AU - Makuch,Wioletta, AU - Przewlocka,Barbara, Y1 - 2008/07/22/ PY - 2008/04/02/received PY - 2008/07/14/revised PY - 2008/07/14/accepted PY - 2008/8/8/pubmed PY - 2009/2/4/medline PY - 2008/8/8/entrez SP - 75 EP - 84 JF - Brain, behavior, and immunity JO - Brain Behav Immun VL - 23 IS - 1 N2 - We have previously demonstrated that glial inhibitors reduce the development of allodynia and hyperalgesia, potentiating the effect of a single morphine dose in a neuropathic pain model. This study explores the effects of two glial activation inhibitors, minocycline and pentoxifylline, on the development of tolerance to morphine in naive and chronic constriction injury (CCI)-exposed mice. Administration of morphine to naive (20 mg/kg; i.p.) and CCI-exposed mice (40 mg/kg; i.p.) twice daily resulted in tolerance to its anti-nociceptive effect after 6 days. Injections of morphine were combined with minocycline (30 mg/kg, i.p.) or pentoxifylline (20 mg/kg, i.p.) administered as two preemptive doses before first morphine administration in naive or pre-injury in CCI-exposed mice, and repeated twice daily 30 min before each morphine administration. With treatment, development of morphine tolerance was delayed by 5 days (from 6 to 11 days), as measured by the tail-flick test in naive and by tail-flick, von Frey, and cold plate tests in CCI-exposed mice. Western blot analysis of CD11b/c and GFAP protein demonstrated that minocycline and pentoxifylline, at doses delaying development of tolerance to morphine analgesia, significantly diminished the morphine-induced increase in CD11b/c protein level. We found that repeated systemic administration of glial inhibitors significantly delays development of morphine tolerance by attenuating the level of this microglial marker under normal and neuropathic pain conditions. Our results support the idea that targeting microglial activation during morphine therapy/treatment is a novel and clinically promising method for enhancing morphine's analgesic effects, especially in neuropathic pain. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/18684397/Attenuation_of_morphine_tolerance_by_minocycline_and_pentoxifylline_in_naive_and_neuropathic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(08)00310-3 DB - PRIME DP - Unbound Medicine ER -