In this study, the expression and functional role of metallothioneins I and II (MT-I/II) were evaluated in the spinal cord in rat models of inflammatory and neuropathic pain. Complete Freund's adjuvant (CFA) injection into the hindpaw induced an increase in MT-I/II protein expression in bilateral dorsal and ventral horns throughout the spinal cord, while chronic constriction injury (CCI) of the sciatic nerve induced an increase in MT-I/II expression in the ipsilateral dorsal and ventral horns of the lower lumbar spinal cord. Increased MT-I/II immunoreactivity was predominantly localized to vascular endothelial cells. CFA injection- and CCI-induced MT-I/II expression was inhibited by intrathecal administration of MT-I siRNA. Treatment with MT-I siRNA before CFA injection or at early time points after CCI resulted in a significant attenuation of mechanical allodynia and thermal hyperalgesia, while treatment at later time points had no effect on established pain behaviors. Our results suggest that endogenous MT-I/II might play an important role in the pathogenesis of pain behaviors, participating in the initiation of inflammatory and neuropathic pain rather than in their maintenance.
Keywords: ANOVA; BBB; BSCB; CCI; CFA; COX-2; Endothelial cell; GLT1; ICAMs; IL; Inflammatory pain; L; MM RNA; MTs; Metallothionein; Neuropathic pain; PECAMs; RT-PCR; SEM; Spinal cord; analysis of variance; blood-brain barrier; blood-spinal cord barrier; chronic constriction injury; complete Freund's adjuvant; cyclooxygenase-2; glucose transporter 1; intercellular adhesion molecules; interleukin; lumbar; metallothioneins; mismatch RNA; platelet-endothelial cellular adhesion molecules; reverse transcription-polymerase chain reaction; standard errors of the mean.
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