Substance P Research & Studies

Mice lacking two neuropeptides thought to be essential for processing pain show no change in how they respond to a wide range of harmful stimuli.

Substance P (SP) is an 11-amino acid-long neuropeptide expressed by the central nervous system (CNS), the peripheral nervous system, and immune cells. SP is a member of the tachykinin (TAC) family of neuropeptides encoded by the TAC1 gene. SP elicits its activity via interacting with the G protein-coupled neurokinin receptors (NKRs), including NK1R, NK2R, and NK3R. NKRs are expressed on the surface of various cell types, including the blood vessels and lymphatics endothelial cells, immune cells, fibroblasts, and neurons. Activation of NKRs stimulates inositol trisphosphate/diacylglycerol (IP3/DAG) and cyclic adenosine monophosphate (cAMP) second messenger in a cell context-dependent manner. Activation of NKRs mediates complex neuronal signaling pathways linked to sensations and emotional responses. Emerging evidence suggests that substance P plays other vital roles in inflammation, wound healing, and angiogenesis. Agents that inhibit substance P activity are currently being investigated as potential drugs for pain relief and other clinical conditions.

Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.

Substance P (SP), a neuropeptide and pain transmitter has multiple roles and is involved in various processes in the body [...].

Substance P (SP) is an undecapeptide encoding the tachykinin 1 (TAC1) gene and belongs to the tachykinin family. SP is widely distributed in the central nervous system and the peripheral nervous system. SP is also produced by nonneuronal cells, such as inflammatory cells and endothelial cells. The biological activities of SP are mainly regulated through the high-affinity neurokinin 1 receptor (NK-1R). The SP/NK-1R system plays an important role in the molecular bases of many human pathophysiologic processes, such as pain, infectious and inflammatory diseases, and cancer. In addition, this system has been implicated in fibrotic diseases and processes such as wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, and lung fibrosis. Recently, studies have shown that SP plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of fibrosis. NK-1R receptor antagonists could provide clinical solutions for fibrotic diseases. This review summarizes the structure and function of SP and its involvement in fibrotic diseases.

Substance P has recently received much attention as a mediator of adverse heart remodelling and cardiac inflammation by releasing proinflammatory cytokines and matrix metalloproteases from immune and cardiac mast cells. Based on animal models, Substance P is highly associated with the development of cardiomyopathies, subsequently leading to heart failure. After a brief overview of the pathological role of Substance P in cardiac remodelling and cardiac inflammation, this review summarizes the limited, existing data of Substance P blood levels in adults with cardiovascular diseases, demonstrating a high variability of blood concentrations. The investigation of blood levels led to the conclusion that variability is mainly caused by differences in blood sampling and determination. Furthermore, this review illustrates alternate strategies to investigate human Substance P levels as deeper knowledge of them enables further insights into the potential role of Substance P in cardiovascular diseases.

Substance P (SP) is a highly conserved member of the tachykinin peptide family that is widely expressed throughout the animal kingdom. The numerous members of the tachykinin peptide family are involved in a multitude of neuronal signaling pathways, mediating sensations and emotional responses (Steinhoff et al. in Physiol Rev 94:265-301, 2014). In contrast to receptors for classical transmitters, such as glutamate (Parsons et al. in Handb Exp Pharmacol 249-303, 2005), only a minority of neurons in certain brain areas express neurokinin receptors (NKRs) (Mantyh in J Clin Psychiatry 63:6-10, 2002). SP is also expressed by a variety of non-neuronal cell types such as microglia, as well as immune cells (Mashaghi et al. in Cell Mol Life Sci 73:4249-4264, 2016). SP is an 11-amino acid neuropeptide that preferentially activates the neurokinin-1 receptor (NK1R). It transmits nociceptive signals via primary afferent fibers to spinal and brainstem second-order neurons (Cao et al. in Nature 392:390-394, 1998). Compounds that inhibit SP's action are being investigated as potential drugs to relieve pain. More recently, SP and NKR have gained attention for their role in complex psychiatric processes. It is a key goal in the field of pain research to understand mechanisms involved in the transition between acute pain and chronic pain. The influence of emotional and cognitive inputs and feedbacks from different brain areas makes pain not only a perception but an experience (Zieglgänsberger et al. in CNS Spectr 10:298-308, 2005; Trenkwaldner et al. Sleep Med 31:78-85, 2017). This review focuses on functional neuronal plasticity in spinal dorsal horn neurons as a major relay for nociceptive information.

Epilepsy is a common neurological disease characterized by abnormal temporary discharge of neurons in the central nervous system. In recent years, studies have revealed the localization and changes in the density of neuropeptides, such as substance P (SP) in the pathogenesis of epilepsy. This review is a concise overview of SP and their physiologic and pathologic functions on regulating epilepsy, and the underline mechanisms.

Substance P is a decapeptide which forms part of the group known as neuropeptides, that is, peptides released by some neurones such as the slow-conducting C fibres and the rapid-conducting A-delta fibres. These neurones belong to the category of non-adrenergic non-cholinergic nerves (NANC), which perform their action through a mechanism known as "axonic reflex". This mechanism is an antidromic stimulation which produces a secretion of neuropeptides, especially substance P. It is known that substance P, once released, is able to exert a number of actions including among others inflammatory and bronchospastic activities and a stimulation of the immunologic system. Other effects attributed to this substance are an increase in capillary permeability and oedema and the perpetuation of certain conditions such as asthma, rhinitis and chronic urticaria or hives. The production, metabolism and actions of this neuropeptide are described.