Review
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World J Anesthesiol. Mar 27, 2014; 3(1): 71-81
Published online Mar 27, 2014. doi: 10.5313/wja.v3.i1.71
Molecular mechanism of inflammatory pain
Yeu-Shiuan Su, Wei-Hsin Sun, Chih-Cheng Chen
Yeu-Shiuan Su, Wei-Hsin Sun, Department of Life Sciences, National Central University, Jhongli 32054, Taiwan
Chih-Cheng Chen, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
Chih-Cheng Chen, Taiwan Mouse Clinic-National Phenotyping and Drug Testing Center, Academia Sinica, Taipei 115, Taiwan
Author contributions: Su YS and Sun WH contributed equally to this work, collected literatures, and wrote the manuscript; Chen CC designed the scope of the minireview and wrote the manuscript.
Correspondence to: Chih-Cheng Chen, PhD, Institute of Biomedical Sciences, Academia Sinica, 128 Academia Road, Section 2, Taipei 115, Taiwan. chih@ibms.sinica.edu.tw
Telephone: +886-2-26523917 Fax: +886-2-27829224
Received: June 29, 2013
Revised: September 27, 2013
Accepted: November 1, 2013
Published online: March 27, 2014
Abstract

Chronic inflammatory pain resulting from arthritis, nerve injury and tumor growth is a serious public health issue. One of the major challenges in chronic inflammatory pain research is to develop new pharmacologic treatments with long-term efficacy and few side effects. The mediators released from inflamed sites induce complex changes in peripheral and central processing by directly acting on transducer receptors located on primary sensory neurons to transmit pain signals or indirectly modulating pain signals by activating receptors coupled with G-proteins and second messengers. High local proton concentration (acidosis) is thought to be a decisive factor in inflammatory pain and other mediators such as prostaglandin, bradykinin, and serotonin enhance proton-induced pain. Proton-sensing ion channels [transient receptor potential V1 (TRPV1) and the acid-sensing ion channel (ASIC) family] are major receptors for direct excitation of nociceptive sensory neurons in response to acidosis or inflammation. G-protein-coupled receptors activated by prostaglandin, bradykinin, serotonin, and proton modulate functions of TRPV1, ASICs or other ion channels, thus leading to inflammation- or acidosis-linked hyperalgesia. Although detailed mechanisms remain unsolved, clearly different types of pain or hyperalgesia could be due to complex interactions between a distinct subset of inflammatory mediator receptors expressed in a subset of nociceptors. This review describes new directions for the development of novel therapeutic treatments in pain.

Keywords: Acid-sensing ion channel, Acidosis, G-protein-coupled receptor, Inflammation, Proton-sensing ion channel, Transient receptor potential V1

Core tip: Tissue acidosis that occurs during inflammation is central to the development and maintenance of chronic pain. Recent studies have revealed a variety of proton-sensing ion channels (e.g., acid-sensing ion channels, transient receptor potential V1) and G-protein-coupled receptors (e.g., G2 accumulation 2A, G-protein-coupled receptor 4, ovarian cancer G-protein-coupled receptor, T-cell death-associated gene 8) responsible for acid-induced pain. These cell-surface membrane proteins are promising therapeutic targets for the development of new analgesic drugs for chronic inflammatory pain.