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Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation.
Pain. 2005 May; 115(1-2):71-83.PAIN

Abstract

Activated glial cells (microglia and astroglia) in the spinal cord play a major role in mediating enhanced pain states by releasing proinflammatory cytokines and other substances thought to facilitate pain transmission. In the present study, we report that intrathecal administration of minocycline, a selective inhibitor of microglial cell activation, inhibits low threshold mechanical allodynia, as measured by the von Frey test, in two models of pain facilitation. In a rat model of neuropathic pain induced by sciatic nerve inflammation (sciatic inflammatory neuropathy, SIN), minocycline delayed the induction of allodynia in both acute and persistent paradigms. Moreover, minocycline was able to attenuate established SIN-induced allodynia 1 day, but not 1 week later, suggesting a limited role of microglial activation in more perseverative pain states. Our data are consistent with a crucial role for microglial cells in initiating, rather than maintaining, enhanced pain responses. In a model of spinal immune activation by intrathecal HIV-1 gp120, we show that the anti-allodynic effects of minocycline are associated with decreased microglial activation, attenuated mRNA expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-1beta-converting enzyme, TNF-alpha-converting enzyme, IL-1 receptor antagonist and IL-10 in lumbar dorsal spinal cord, and reduced IL-1beta and TNF-alpha levels in the CSF. In contrast, no significant effects of minocycline were observed on gp120-induced IL-6 and cyclooxygenase-2 expression in spinal cord or CSF IL-6 levels. Taken together these data highlight the importance of microglial activation in the development of exaggerated pain states.

Authors+Show Affiliations

Department of Psychology and the Center for Neuroscience, University of Colorado at Boulder, Campus Box 345, Boulder, CO 80309-0345, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15836971

Citation

Ledeboer, Annemarie, et al. "Minocycline Attenuates Mechanical Allodynia and Proinflammatory Cytokine Expression in Rat Models of Pain Facilitation." Pain, vol. 115, no. 1-2, 2005, pp. 71-83.
Ledeboer A, Sloane EM, Milligan ED, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain. 2005;115(1-2):71-83.
Ledeboer, A., Sloane, E. M., Milligan, E. D., Frank, M. G., Mahony, J. H., Maier, S. F., & Watkins, L. R. (2005). Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain, 115(1-2), 71-83.
Ledeboer A, et al. Minocycline Attenuates Mechanical Allodynia and Proinflammatory Cytokine Expression in Rat Models of Pain Facilitation. Pain. 2005;115(1-2):71-83. PubMed PMID: 15836971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. AU - Ledeboer,Annemarie, AU - Sloane,Evan M, AU - Milligan,Erin D, AU - Frank,Matthew G, AU - Mahony,John H, AU - Maier,Steven F, AU - Watkins,Linda R, PY - 2004/05/13/received PY - 2004/12/06/revised PY - 2005/02/07/accepted PY - 2005/4/20/pubmed PY - 2005/6/29/medline PY - 2005/4/20/entrez SP - 71 EP - 83 JF - Pain JO - Pain VL - 115 IS - 1-2 N2 - Activated glial cells (microglia and astroglia) in the spinal cord play a major role in mediating enhanced pain states by releasing proinflammatory cytokines and other substances thought to facilitate pain transmission. In the present study, we report that intrathecal administration of minocycline, a selective inhibitor of microglial cell activation, inhibits low threshold mechanical allodynia, as measured by the von Frey test, in two models of pain facilitation. In a rat model of neuropathic pain induced by sciatic nerve inflammation (sciatic inflammatory neuropathy, SIN), minocycline delayed the induction of allodynia in both acute and persistent paradigms. Moreover, minocycline was able to attenuate established SIN-induced allodynia 1 day, but not 1 week later, suggesting a limited role of microglial activation in more perseverative pain states. Our data are consistent with a crucial role for microglial cells in initiating, rather than maintaining, enhanced pain responses. In a model of spinal immune activation by intrathecal HIV-1 gp120, we show that the anti-allodynic effects of minocycline are associated with decreased microglial activation, attenuated mRNA expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-1beta-converting enzyme, TNF-alpha-converting enzyme, IL-1 receptor antagonist and IL-10 in lumbar dorsal spinal cord, and reduced IL-1beta and TNF-alpha levels in the CSF. In contrast, no significant effects of minocycline were observed on gp120-induced IL-6 and cyclooxygenase-2 expression in spinal cord or CSF IL-6 levels. Taken together these data highlight the importance of microglial activation in the development of exaggerated pain states. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/15836971/Minocycline_attenuates_mechanical_allodynia_and_proinflammatory_cytokine_expression_in_rat_models_of_pain_facilitation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(05)00058-8 DB - PRIME DP - Unbound Medicine ER -