Pain is a physiological response to bodily damage and serves as a warning of potential threat.
Pain can also transform from an acute response to noxious stimuli to a
chronic condition with notable emotional and psychological components that requires treatment. Indeed, the management of chronic
pain is currently an important unmet societal need. Several reports have implicated the release of the
neurotransmitter adenosine triphosphate (
ATP) and subsequent activation of
purinergic receptors in distinct
pain etiologies.
Purinergic receptors are broadly expressed in peripheral neurons and the spinal cord; thus, purinergic signaling in sensory neurons or in spinal circuits may be critical for
pain processing. Nevertheless, an outstanding question remains: what are the mechanisms of
ATP release that initiate nociceptive signaling?
Connexin and pannexin channels are established conduits of
ATP release and have been suggested to play important roles in a variety of pathologies, including several models of
pain. As such, these large-pore channels represent a new and exciting putative pharmacological target for
pain treatment. Herein, we will review the current evidence for a role of
connexin and pannexin channels in
ATP release during nociceptive signaling, such as neuropathic and inflammatory
pain. Collectively, these studies provide compelling evidence for an important role of
connexins and pannexins in
pain processing.