There is growing evidence that nociceptor neurons can significantly impact the immune system and inflammation. Thus, aside from being a primary feature of inflammation, pain is also integral to regulating immunity. Nociceptors are capable of releasing neuropeptides and neurotransmitters which act to regulate the vascular system and the innate and adaptive immunity. These neuronal mediators are recognized by immune cells, including dendritic cells, neutrophils, macrophages, mast cells, and T cells, which makes them able to respond directly to nociceptors. T cells or macrophages were demonstrated to sensitize nociceptors by releasing IL-17A. Macrophages and monocytes have been extensively implicated in chronic pain. It has been shown that neutrophils might migrate to inflamed tissues and cause pain by releasing cytokines and prostaglandin E2 (PGE2) in carrageenan-induced inflammatory pain and neuropathy. CD11b+ myeloid cells (potentially macrophages) are found to induce postoperative pain following incisional wound injury. Inflammatory cells can increase pain by directly acting on nociceptor neurons with pro-inflammatory cytokines, growth factors, and lipids.
Recent research also reveals that nociceptors play important role in regulating lung, skin, joint and gastrointestinal disorders, and targeting pain could also treat inflammation. For example, asthma is caused by a sensitivity to nociceptors, which leads to hyperreactivity in the lungs and airways. Nociceptor neurons also are important in regulating inflammation in gastrointestinal diseases. Notably, pulmonary neuroendocrine cells (PNECs) are sensory organoids that include innervated epithelial cells that can produce CGRP, innervated by nociceptors. PNEC dysfunction may cause abnormal CGRP release and immune cell recruitment in lung diseases. As neuron cells could regulate immune function, neurons were reported to have a suppressing effect on immune responses for maintaining homeostasis and even preventing the development of autoimmunity. For example, denervation was reported to decrease joint swelling and intense pain in rheumatoid arthritis in human and animal studies, a process that may be due to nerve-vascular interactions. Furthermore, cartilage antibody immune complexes have been reported to trigger pain in RA via activation of Fc? receptor I on nociceptors. Therefore, the identification of autoantibodies in developing persistent pain may not only aid in relieving pain in RA, but also for pain in other diseases associated with autoantibody production, such as Sjögren’s syndrome, systemic lupus erythematosus, and Guillain–Barré syndrome.
Increasingly, it is evident that nociceptor neuron-immune interactions are crucial to pain and inflammation. Dysregulation of these interactions could contribute to the pathogenesis of several inflammatory diseases, including those affecting the skin, joints, respiratory system, and digestive tract. As well as in peripheral tissue damaged by injury, these neuro-immune interactions were observed in the central nervous system. Understanding interactions between nociceptor, immune cells, and glial cells could reveal new mechanisms of inflammatory disorders and develop new therapeutics to treat and prevent inflammatory diseases and chronic pain.
We welcome the submission of Original Research and Review articles, which cover, but are not limited to, the following topics:
1. Interaction of the nociceptor and different immune cells.
2. Immune cell-derived cytokines, lipids, proteases, and growth factors sensed by nociceptor neurons.
3. Neuropeptides and neurotransmitters released from nociceptors and sensed by innate and adaptive immune cells.
4. Inflammatory and neurological autoimmune diseases driven by dysregulated neuron-immune interactions.
There is growing evidence that nociceptor neurons can significantly impact the immune system and inflammation. Thus, aside from being a primary feature of inflammation, pain is also integral to regulating immunity. Nociceptors are capable of releasing neuropeptides and neurotransmitters which act to regulate the vascular system and the innate and adaptive immunity. These neuronal mediators are recognized by immune cells, including dendritic cells, neutrophils, macrophages, mast cells, and T cells, which makes them able to respond directly to nociceptors. T cells or macrophages were demonstrated to sensitize nociceptors by releasing IL-17A. Macrophages and monocytes have been extensively implicated in chronic pain. It has been shown that neutrophils might migrate to inflamed tissues and cause pain by releasing cytokines and prostaglandin E2 (PGE2) in carrageenan-induced inflammatory pain and neuropathy. CD11b+ myeloid cells (potentially macrophages) are found to induce postoperative pain following incisional wound injury. Inflammatory cells can increase pain by directly acting on nociceptor neurons with pro-inflammatory cytokines, growth factors, and lipids.
Recent research also reveals that nociceptors play important role in regulating lung, skin, joint and gastrointestinal disorders, and targeting pain could also treat inflammation. For example, asthma is caused by a sensitivity to nociceptors, which leads to hyperreactivity in the lungs and airways. Nociceptor neurons also are important in regulating inflammation in gastrointestinal diseases. Notably, pulmonary neuroendocrine cells (PNECs) are sensory organoids that include innervated epithelial cells that can produce CGRP, innervated by nociceptors. PNEC dysfunction may cause abnormal CGRP release and immune cell recruitment in lung diseases. As neuron cells could regulate immune function, neurons were reported to have a suppressing effect on immune responses for maintaining homeostasis and even preventing the development of autoimmunity. For example, denervation was reported to decrease joint swelling and intense pain in rheumatoid arthritis in human and animal studies, a process that may be due to nerve-vascular interactions. Furthermore, cartilage antibody immune complexes have been reported to trigger pain in RA via activation of Fc? receptor I on nociceptors. Therefore, the identification of autoantibodies in developing persistent pain may not only aid in relieving pain in RA, but also for pain in other diseases associated with autoantibody production, such as Sjögren’s syndrome, systemic lupus erythematosus, and Guillain–Barré syndrome.
Increasingly, it is evident that nociceptor neuron-immune interactions are crucial to pain and inflammation. Dysregulation of these interactions could contribute to the pathogenesis of several inflammatory diseases, including those affecting the skin, joints, respiratory system, and digestive tract. As well as in peripheral tissue damaged by injury, these neuro-immune interactions were observed in the central nervous system. Understanding interactions between nociceptor, immune cells, and glial cells could reveal new mechanisms of inflammatory disorders and develop new therapeutics to treat and prevent inflammatory diseases and chronic pain.
We welcome the submission of Original Research and Review articles, which cover, but are not limited to, the following topics:
1. Interaction of the nociceptor and different immune cells.
2. Immune cell-derived cytokines, lipids, proteases, and growth factors sensed by nociceptor neurons.
3. Neuropeptides and neurotransmitters released from nociceptors and sensed by innate and adaptive immune cells.
4. Inflammatory and neurological autoimmune diseases driven by dysregulated neuron-immune interactions.
