Figure 6.

Effects of intrathecal injection of the microglial inhibitor minocycline (A), specific β-endorphin antiserum (B, C), and specific opioid receptor antagonist naloxone (D–F) on spinal exenatide antinociception in peripheral neuropathy-induced mechanical allodynia or formalin-induced hyperalgesia in rats. For neuropathic rats, paw withdrawal thresholds were measured by electronic von Frey filaments 2 weeks after tight ligation of L5–L6 spinal nerves. For the formalin test, rats received two intrathecal treatments 30 min before subcutaneous injection of 50 μl of 5% formalin. Nociceptive behavior was quantified by counting the number of the formalin-injected paw flinches in 1 min epochs. Blank serum as the negative control was from a healthy rabbit without any treatment. G, Effects of intrathecal injection of exenatide on the spinal β-endorphin level in neuropathic rats and sham rats. Minocycline (100 μg) was intrathecally injected 4 h earlier before exenatide treatment. Ipsilateral spinal lumbar enlargements were obtained 1 h after exenatide injection in neuropathic rats. H, Effects of exenatide (10⁻⁸ m) on β-endorphin release at 2 h after application in primarily cultured spinal microglia, astrocytes, and neurons from the spinal dorsal horn of neonatal rats. β-Endorphin levels in the spinal cord homogenates and culture media were determined by a specific fluorescent immunoassay kit. Data are means ± SEM (n = 6 in each group). ^a,bStatistical significance compared with the saline control and the exenatide group, respectively (p < 0.05 by one-way or two-way ANOVA followed by post hoc Student-Newman-Keuls test).^cStatistical significance compared with the saline control in sham rats (p < 0.05 by one- or two-way ANOVA followed by post hoc Student-Newman-Keuls test).