Involvement of P2X7 receptors in chronic pain disorders

Abstract

Chronic pain is caused by cellular damage with an obligatory inflammatory component. In response to noxious stimuli, high levels of ATP leave according to their concentration gradient, the intracellular space through discontinuities generated in the plasma membrane or diffusion through pannexin-1 hemichannels, and activate P2X7Rs localized at peripheral and central immune cells. Because of the involvement of P2X7Rs in immune functions and especially the initiation of macrophage/microglial and astrocytic secretion of cytokines, chemokines, prostaglandins, proteases, reactive oxygen, and nitrogen species as well as the excitotoxic glutamate/ATP, this receptor type has a key role in chronic pain processes. Microglia are equipped with a battery of pattern recognition receptors that detect pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) from bacterial infections or danger associated molecular patterns (DAMPs) such as ATP. The co-stimulation of these receptors leads to the activation of the NLRP3 inflammasome and interleukin-1β (IL-1β) release. In the present review, we invite you to a journey through inflammatory and neuropathic pain, primary headache, and regulation of morphine analgesic tolerance, in the pathophysiology of which P2X7Rs are centrally involved. P2X7R bearing microglia and astrocyte-like cells playing eminent roles in chronic pain will be also discussed.

Olfactory Ensheathing Cells Alleviate Facial Pain in Rats with Trigeminal Neuralgia by Inhibiting the Expression of P2X7 Receptor

“…The P2X7R fluorescence intensity of each group was analyzed by Image J. P2X7R is mainly expressed by glial cells, especially astrocytes, in the nervous system. Therefore, P2X7R in the TG sections were co-labeled with GFAP for immunofluorescence detection [ 31 , 32 ]. P2X7R and GFAP were observed to be co-located in the TG sections of the rats.…”

Purinergic P2X7 Receptor-mediated inflammation precedes PTSD-related Behaviors in Rats

“…In addition to a role in pain disorders [39][40][41], a growing literature points to the importance of P2X7Rs in stress-induced behavioral changes. Our results suggest that SPS activates P2X7Rs to induce a PTSD-like phenotype in male and female rats.…”

The Role of Microglial Purinergic Receptors in Pain Signaling

“…P2X7 receptor knockout mice exhibit reduced pain hypersensitivity in a model of neuropathic pain [ 89 ]. Blockade of P2X7 receptors significantly reduces nociception in animal models of chronic neuropathic and inflammatory pain [ 90 , 91 ]. Rodent models of chronic inflammatory pain show alleviation of pain by P2X7 receptor antagonists, such as oxidized ATP, A-740003, and A-438079 [ 92 , 93 , 94 ].…”