Antinociceptive Evaluation of Ceftriaxone and Minocycline Alone and in Combination in a Neuropathic Pain Model in Rat Publisher Pubmed



Amin B¹ ; Hajhashemi V¹ ; Hosseinzadeh H² ; Abnous K^{3, 4} Show Affiliations
Source: Neuroscience Published:2012

Abstract

Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. So far, there has been insufficient data on the relationship between glutamate transporters and cytokines in neuropathic pain. This investigation was designed to evaluate the interaction between co-administration of ceftriaxone, a specific GLT1 activator and minocycline, a specific microglia inhibitor, on the mechanical and cold allodynia of chronic constriction injury model (CCI) in rats. Moreover, alteration of the spinal concentration of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was studied. Ceftriaxone (100, 150 and 200. mg/kg, i.p.) and minocycline (25, 50 and 100. mg/kg, i.p.) were administered either alone or in combination for 7 days. Gabapentin (100. mg/kg, i.p.) was selected as a reference drug. Behavioral evaluations were performed 1 day before and on days 3, 5, 7, 10 and 14 after surgery. Each of drugs produced a dose-dependent reversal of the neuropathic pain behaviors. Area under the curve (AUC) of combination therapy revealed that minocycline potentiated cold and mechanical antiallodynic effects of ceftriaxone. TNF-α and IL-1β increased in the spinal cord of CCI animals on days 3, 7 and 14 post-surgery. Production of studied cytokines was significantly attenuated after treatment with ceftriaxone alone and in combination with minocycline compared with control group. It is suggested that combination of these classes of drugs would be a promising approach for treatment of chronic neuropathic pain. © 2012 IBRO.