Protease-activated receptor 2 signalling pathways: a role in pain processing

Introduction: Pain is a complex biological phenomenon that includes intricate neurophysiological, behavioural, psychosocial and affective components. Despite decades of pain research, many patients continue suffering from chronic pain that may be refractory to current medical regimens. Accumulating evidence has indicated an important role of protease-activated receptor 2 (PAR2) in the pathogenesis of pain, including inflammation, neuropathic and cancer pain. Areas covered: In this review, the role of the PAR2 signalling pathway in pain processes, basic mechanism of PAR2 activation and expression of PAR2 in the nervous system is covered. Furthermore, intracellular signalling pathways that are activated by PAR2 are also described. Expert opinion: The role of PAR2 in pain processing is becoming increasingly clear, and although causal implication remains to be established, PAR2 activation has been observed in several disease model systems. Since PAR2 is activated after nerve injury as well as by trypsin and related serine proteases, and PAR2 plays an important role in pain development and maintenance, exploring PAR2 and its corresponding signalling pathways will provide unfathomable knowledge in understanding the molecular basis of pain. This will also help to identify new targets for pharmacological intervention; however, in the context of potential PAR2-directed therapies, several aspects should be clarified.