Sonic Hedgehog Signaling Pathway: A Role in Pain Processing.

Pain, as one of the most prevalent clinical symptoms, is a complex physiological and psychological activity. Long-term severe pain can become unbearable to the body. However, existing treatments do not provide satisfactory results. Therefore, new mechanisms and therapeutic targets need to be urgently explored for pain management. The Sonic hedgehog (Shh) signaling pathway is crucial in embryonic development, cell differentiation and proliferation, and nervous system regulation. Here, we review the recent studies on the Shh signaling pathway and its action in multiple pain-related diseases. The Shh signaling pathway is dysregulated under various pain conditions, such as pancreatic cancer pain, bone cancer pain, chronic post-thoracotomy pain, pain caused by degenerative lumbar disc disease, and toothache. Further studies on the Shh signaling pathway may provide new therapeutic options for pain patients.

Dysregulation of sphingolipid metabolism in pain.

Pain is a clinical condition that is currently of great concern and is often caused by tissue or nerve damage or occurs as a concomitant symptom of a variety of diseases such as cancer. Severe pain seriously affects the functional status of the body. However, existing pain management programs are not fully satisfactory. Therefore, there is a need to delve deeper into the pathological mechanisms underlying pain generation and to find new targets for drug therapy. Sphingolipids (SLs), as a major component of the bilayer structure of eukaryotic cell membranes, also have powerful signal transduction functions. Sphingolipids are abundant, and their intracellular metabolism constitutes a huge network. Sphingolipids and their various metabolites play significant roles in cell proliferation, differentiation, apoptosis, etc., and have powerful biological activities. The molecules related to sphingolipid metabolism, mainly the core molecule ceramide and the downstream metabolism molecule sphingosine-1-phosphate (S1P), are involved in the specific mechanisms of neurological disorders as well as the onset and progression of various types of pain, and are closely related to a variety of pain-related diseases. Therefore, sphingolipid metabolism can be the focus of research on pain regulation and provide new drug targets and ideas for pain.

Role of autophagy in the pathogenesis and regulation of pain.

Pain is a ubiquitous and highly concerned clinical symptom, usually caused by peripheral or central nervous injury, tissue damage, or other diseases. The long-term existence of pain can seriously affect daily physical function and quality of life and produce great torture on the physiological and psychological levels. However, the complex pathogenesis of pain involving molecular mechanisms and signaling pathways has not been fully elucidated, and managing pain remains highly challenging. As a result, finding new targets to pursue effective and long-term pain treatment strategies is required and urgent. Autophagy is an intracellular degradation and recycling process that maintains tissue homeostasis and energy supply, which can be cytoprotective and is vital in maintaining neural plasticity and proper nervous system function. Much evidence has shown that autophagy dysregulation is linked to the emergence of neuropathic pain, such as postherpetic neuralgia and cancer-related pain. Autophagy has also been connected to pain caused by osteoarthritis and lumbar disc degeneration. It is worth noting that in recent years, studies on traditional Chinese medicine have also proved that several traditional Chinese medicine monomers involve autophagy in the mechanism of pain relief. Therefore, autophagy can serve as a potential regulatory target to provide new ideas and inspiration for pain management.