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Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy.
J Pharmacol Exp Ther. 2003 Aug; 306(2):624-30.JP

Abstract

Microglia, the intrinsic macrophages of the central nervous system, have previously been shown to be activated in the spinal cord in several rat mononeuropathy models. Activation of microglia and subsequent release of proinflammatory cytokines are known to play a role in inducing a behavioral hypersensitive state (hyperalgesia and allodynia) in these animals. The present study was undertaken to determine whether minocycline, an inhibitor of microglial activation, could attenuate both the development and existing mechanical allodynia and hyperalgesia in an L5 spinal nerve transection model of neuropathic pain. In a preventive paradigm (to study the effect on the development of hypersensitive behaviors), minocycline (10, 20, or 40 mg/kg intraperitoneally) was administered daily, beginning 1 h before nerve transection. This regimen produced a decrease in mechanical hyperalgesia and allodynia, with a maximum inhibitory effect observed at the dose of 20 and 40 mg/kg. The attenuation of the development of hyperalgesia and allodynia by minocycline was associated with an inhibitory action on microglial activation and suppression of proinflammatory cytokines at the L5 lumbar spinal cord of the nerveinjured animals. The effect of minocycline on existing allodynia was examined after its intraperitoneal administration initiated on day 5 post-L5 nerve transection. Although the postinjury administration of minocycline significantly inhibited microglial activation in neuropathic rats, it failed to attenuate existing hyperalgesia and allodynia. These data demonstrate that inhibition of microglial activation attenuated the development of behavioral hypersensitivity in a rat model of neuropathic pain but had no effect on the treatment of existing mechanical allodynia and hyperalgesia.

Authors+Show Affiliations

Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12734393

Citation

Raghavendra, Vasudeva, et al. "Inhibition of Microglial Activation Attenuates the Development but Not Existing Hypersensitivity in a Rat Model of Neuropathy." The Journal of Pharmacology and Experimental Therapeutics, vol. 306, no. 2, 2003, pp. 624-30.
Raghavendra V, Tanga F, DeLeo JA. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J Pharmacol Exp Ther. 2003;306(2):624-30.
Raghavendra, V., Tanga, F., & DeLeo, J. A. (2003). Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. The Journal of Pharmacology and Experimental Therapeutics, 306(2), 624-30.
Raghavendra V, Tanga F, DeLeo JA. Inhibition of Microglial Activation Attenuates the Development but Not Existing Hypersensitivity in a Rat Model of Neuropathy. J Pharmacol Exp Ther. 2003;306(2):624-30. PubMed PMID: 12734393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. AU - Raghavendra,Vasudeva, AU - Tanga,Flobert, AU - DeLeo,Joyce A, Y1 - 2003/05/06/ PY - 2003/5/8/pubmed PY - 2003/8/29/medline PY - 2003/5/8/entrez SP - 624 EP - 30 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 306 IS - 2 N2 - Microglia, the intrinsic macrophages of the central nervous system, have previously been shown to be activated in the spinal cord in several rat mononeuropathy models. Activation of microglia and subsequent release of proinflammatory cytokines are known to play a role in inducing a behavioral hypersensitive state (hyperalgesia and allodynia) in these animals. The present study was undertaken to determine whether minocycline, an inhibitor of microglial activation, could attenuate both the development and existing mechanical allodynia and hyperalgesia in an L5 spinal nerve transection model of neuropathic pain. In a preventive paradigm (to study the effect on the development of hypersensitive behaviors), minocycline (10, 20, or 40 mg/kg intraperitoneally) was administered daily, beginning 1 h before nerve transection. This regimen produced a decrease in mechanical hyperalgesia and allodynia, with a maximum inhibitory effect observed at the dose of 20 and 40 mg/kg. The attenuation of the development of hyperalgesia and allodynia by minocycline was associated with an inhibitory action on microglial activation and suppression of proinflammatory cytokines at the L5 lumbar spinal cord of the nerveinjured animals. The effect of minocycline on existing allodynia was examined after its intraperitoneal administration initiated on day 5 post-L5 nerve transection. Although the postinjury administration of minocycline significantly inhibited microglial activation in neuropathic rats, it failed to attenuate existing hyperalgesia and allodynia. These data demonstrate that inhibition of microglial activation attenuated the development of behavioral hypersensitivity in a rat model of neuropathic pain but had no effect on the treatment of existing mechanical allodynia and hyperalgesia. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12734393/Inhibition_of_microglial_activation_attenuates_the_development_but_not_existing_hypersensitivity_in_a_rat_model_of_neuropathy_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12734393 DB - PRIME DP - Unbound Medicine ER -