Substance P, A Promising Therapeutic Target in Musculoskeletal Disorders

Abstract

A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.

Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy

“…15 This minor concern about severe side effects and the need for the new approach to treat tendinopathy can motivate us to conduct further studies on the use of SPI in humans. 18 We generated and used a rat model of tendinopathy referencing previous studies. 24,31 The overuse injury in tendinopathy was replaced by the injection of collagenase.…”

“…15 This minor concern about severe side effects and the need for the new approach to treat tendinopathy can motivate us to conduct further studies on the use of SPI in humans. 18…”

Vertebral Subluxation and Systems Biology: An Integrative Review Exploring the Salutogenic Influence of Chiropractic Care on the Neuroendocrine-Immune System

“…Although the substance P was originally considered primarily a neurotransmitter and effector of musculoskeletal disorders, it is also a key molecule in neurogenic inflammation response, regulating cell functions by autocrine, paracrine, endocrine, and neuroendocrine mechanisms [ 311 ]. Substance P is secreted and synthesized by nerve cells as well as many types of immune cells, is present in both CSF and blood, and has roles in a diverse array of physiological processes including control of inflammation [ 312 ], regulation of other cytokines particularly in the GI tract [ 313 ], governance of bone homeostasis [ 314 ], regulation of cardiac inflammation [ 315 ], modulation of inflammatory CNS disorders [ 316 ], and it influences anxiety behaviors via effects on the sympathetic nervous system via activation of the HPA axis and subsequent release of cortisol [ 317 ].…”

Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts

“…Since substance P and NK-1R are elevated in models of overuse and in human overuse pathologies, the substance P pathway has been proposed as a therapeutic target for musculoskeletal disorders [24]. In addition to its role in nociception, substance P may also play a role in the development of fibrosis in musculotendinous tissues.…”