Microglial pannexin-1 as a target for joint pain
In this study led by Dr. Tuan Trang, in collaboration with UTCSP member Dr. Steven Prescott and other Canadian colleagues, they sought to determine the role of microglial pannexin-1 (Panx1), a nonselective channel in a rodent model of arthritic joint pain. They found that deletion of Panx1 exclusively from microglia prevented pain behaviour following injection of monosodium iodoacetate (MIA) into the joints. They also found that either intrathecal or systemic injection of Panx1 inhibitors reversed MIA-induced pain behaviour. They next discovered that inhibiting Panx1 decreased the release of the inflammatory cytokine, IL-1b, in the cerebral spinal fluid. Injection of IL-1b intrathecally was sufficient to induce pain behaviour in MIA-injected mice lacking microglial Panx1. Taken together, these results suggest that microglial Panx1 activation mediates IL-1b release in the spinal cord and this pathway underlies joint injury-induced pain.
The final experiment of this study aimed to determine whether Panx1 would be an ideal pharmacological target for treatment of joint pain. Importantly, Mousseau et al. found that the FDA-approved drug, probenecid, a Panx1 inhibitor clinically used to treat gout, reversed joint injury-induced pain behaviour when given systemically. This opens the possibility of the adoption of probenecid, or other Panx1 inhibitors, as potential therapeutic for chronic joint pain.
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Reference: Mousseau, M., Burma, N.E., Lee, K.Y., Leduc-Pessah, H., Kwok, C.H.T., Reid, A.R., O’Brien, M., Sagalajev, B., Stratton, J.A., Patrick, N., et al. (2018). Microglial pannexin-1 channel activation is a spinal determinant of joint pain. Sci. Adv. 4, eaas9846.