substance P - Science topic

Osteoarthritis (OA) is the most prevalent arthritis type globally. The prevalence has been increasing over the last few decades tremendously and this rise is projected to continue to reach a disastrous hike by the end of the 2050. People aged over 50 and in women the disorder is common, however, recent research explore an increasing OA trend in young adults, especially who experiences joint insult in participating contact sports. Researchers continuous efforts explore molecular endophytes in OA pathogenesis, more meticulous explanation is yet to come and get agreed by experts.

OA molecular endophytes come from low-grade synovial inflammation, articular cartilage damage, meniscal lesions, and subchondral bone (SCB) resorption. Molecular endophytes include aggrecanase 1,2, MMPs, proinflammatory cytokines (IL-1, 6, TNF-alpha), NOS, PGE2, COX2, ADAMTS-4,5, etc., are catabolic for extracellular matrix (ECM). Cytokines cause synovial inflammation and induces SCB osteoclastogenesis, bone resorption and bone remodeling. Osteoclastogenesis is associated with neovascularization and neurogenesis that further contribute SCB pain. Osteocastogenesis associated H+, CGRP, bradykinin, PGE2, COX2, NOS, substance P sensitize peripheral nerve and dorsal nerve root contributing generalized body ache in the disorder.

Obesity-dependent mechanical load in the osteochondral unit contribute OA pathogenesis. However, obesity-associated increased adipokines, for example, visfatin and resistin with autocrine, paracrine and endocrine effect contribute local and systemic joint pain, mostly in knee and hand joints with impaired physical function and quality of life. Adiposity with infiltrated inflammatory cells further release profuse proinflammatory cytokine that contribute cartilage destruction and synovial inflammation. In young adult, meniscal injury with increased cytokines may progress to radiographic OA development, hence, early treatment of meniscal lesion is crucial.

All these molecular endophytes initiate intra-cellular signaling cascades, including TGF-β, p38 MAPK, RAF–MEK–ERK, NF-kB, Wnt, and PI3K/AKT/mTOR, and IL-1. Inhibiting one pathway may not be useful in all patients and multiple simultaneous signalling pathways may be active in OA. OA biomolecular changes may vary depending on the predisposing factors. Poor mechanical load management make OA treatment a failure. Certain IA therapies may cause short-term pain relief but at the expense of irreversible chondrotoxicity. All these complicated factors involved in OA pathogenesis make finding a unique solution for the disorder difficult, further research is required.

Dear colleagues,

I would like to ask you some questions regarding your experience or research in the pharmacologic treatment and rehabilitation of infants with dysphagia having absent or immature gag and cough reflex.

Does anybody have experience using spicy foods (capsaicin, piperine) to stimulate cough in these group of patients?

Has anybody tried pharmacologic treatment (e.g., use of substance P)?

What about the use of e-stim (vitalstim or similar)? Or Transcutaneous vagus nerve stimulation?

Thanks in advance