Spinal interleukin-10 produces antinociception in neuropathy through microglial β-endorphin expression, separated from antineuroinflammation

Publication date: Available online 19 June 2018 Source:Brain, Behavior, and Immunity Author(s): Hai-Yun Wu, Xiao-Fang Mao, Xue-Qi Tang, Usman Ali, Evhy Apryani, Hao Liu, Xin-Yan Li, Yong-Xiang Wang Interleukin 10 (IL-10) is antinociceptive in various animal models of pain without induction of tolerance, and its mechanism of action was generally believed to be mediated by inhibition of neuroinflammation. Here we reported that intrathecal IL-10 injection dose dependently attenuated mechanical allodynia and thermal hyperalgesiain male and female neuropathic rats, with ED50 values of 40.8 ng and 24 ng, and Emax values of 61.5% MPE and 100% MPE in male rats. Treatment with IL-10 specifically increased expression of the β-endorphin (but not prodynorphin) gene and protein in primary cultures of spinal microglia but not in astrocytes or neurons. Intrathecal injection of IL-10 stimulated β-endorphin expression from microglia but not neurons or astrocytes in both contralateral and ipsilateral spinal cords of neuropathic rats. However, intrathecal injection of the β-endorphin neutralizing antibody, opioid receptor antagonist naloxone, or μ-opioid receptor antagonist CTAP completely blocked spinal IL-10-induced mechanical antiallodynia, while the microglial inhibitor minocycline and specific microglia depletor reversed spinal IL-10-induced β-endorphin overexpression and mechanical antiallodynia. IL-10 treatment increased spinal microglial STAT3 phosphorylation, and the...
Source: Brain, Behavior, and Immunity - Category: Neurology Source Type: research