Senso-Immunologic Prospects for Complex Regional Pain Syndrome Treatment

Abstract

Complex regional pain syndrome (CRPS) is a chronic pain syndrome that occurs in tissue injuries as the result of surgery, trauma, or ischemia. The clinical features of this severely painful condition include redness and swelling of the affected skin. Intriguingly, it was recently suggested that transient receptor potential ankyrin 1 (TRPA1) is involved in chronic post-ischemia pain, a CRPS model. TRPA1 is a non-selective cation channel expressed in calcitonin gene-related peptide (CGRP)-positive primary nociceptors that becomes highly activated in ischemic conditions, leading to the generation of pain. In this review, we summarize the history of TRPA1 and its involvement in pain sensation, inflammation, and CRPS. Furthermore, bone atrophy is also thought to be a characteristic clinical sign of CRPS. The altered bone microstructure of CRPS patients is thought to be caused by aggravated bone resorption via enhanced osteoclast differentiation and activation. Although TRPA1 could be a target for pain treatment in CRPS patients, we also discuss the paradoxical situation in this review. Nociceptor activation decreases the risk of bone destruction via CGRP secretion from free nerve endings. Thus, TRPA1 inhibition could cause severe bone atrophy. However, the suitable therapeutic strategy is controversial because the pathologic mechanisms of bone atrophy in CRPS are unclear. Therefore, we propose focusing on the remission of abnormal bone turnover observed in CRPS using a recently developed concept: senso-immunology.

Imaging Modalities and Their Findings in Patients With Complex Regional Pain Syndrome: A Review

“…Trauma is associated with varying degrees of peripheral nerve damage, depending on the extent and site of injury [4]. There is also associated sympathetic dysregulation due to inflammatory changes in the tracts [4].…”

“…Trauma is associated with varying degrees of peripheral nerve damage, depending on the extent and site of injury [4]. There is also associated sympathetic dysregulation due to inflammatory changes in the tracts [4]. Figure 1 shows the mechanism by which trauma-induced neuroinflammation can result in abnormally magnified pain sensations.…”

“…It ruins their quality of life and sometimes might also cause physical disability [1,2]. Inflammation and autoimmunity form a very important part of the pathophysiology of this disease [4].…”

Senso-immunology: The Emerging Connection between Pain and Immunity

“…5). 4,58 It is important for physiologists and immunologists to cooperate with each other to promote senso-immunology to develop medical treatments that can improve the complications and prognosis of various inflammatory or painful conditions.…”

Causalgia: a military pain syndrome

“…In addition to motor and sensory dysfunction, change in skin color, and altered temperature sensation, contractures may also occur in the affected limb. 1 The primary etiology of CRPS type II or causalgia is wartime injury, chiefly from powerful missile explosions and penetrating weaponry. 2 Among wounded soldiers, the incidence of causalgia is approximately 1.5%-2% of all peripheral nerve injury cases.…”