About this Research Topic
In order to survive, organisms are required to have the capacity to detect and rapidly neutralize harmful environmental challenges. In complex organisms such as mammals, two systems mediate this function - the immune system and the pain fibers from the somatosensory nervous system. Both systems contain cells that are constitutively present at tissue barriers and that are specialized to detect danger, working as sentinels of body integrity. Not surprisingly, these two systems cross-talk and modulate each other’s activity to generate cellular, molecular and behavioral responses that help to maintain homeostasis. However, If not tightly-controlled, this cross-talk can also be detrimental. Similar to prostaglandins, which are the target of non-steroidal anti-inflammatory drugs (NSAIDs) that are usually used to block inflammatory pain, cytokines are now appreciated as potential targets for pain control due to their capacity to modulate the activity of nociceptive neurons.
Cytokines are inflammatory mediators released mainly by immune cells, but also by non-immune cells, which can directly or indirectly act on nociceptive neurons, mediating pain sensation. For instance, it is well known that IL-1β , TNF-α, IL-6 and IL-17 can bind directly to their receptors expressed by nociceptive fiber terminals leading to neuronal excitability and pain sensation. Moreover, some cytokines can also release different pro-inflammatory mediators such as endothelin; chemokines; leukotrienes and prostaglandins, which can also directly or indirectly induce nociceptor sensitization. Chemokines, such as CXCL1, CCL2, CX3CL1 and their receptors are also pain mediators, facilitating the communication between neuronal and non-neuronal cells at peripheral and central levels.
As mentioned above, these different mediators can modulate pain sensitization via numerous mechanisms, including the activation of downstream signaling pathways (PKA, PKC, MAPK), modulation of ion channels activity as well as upr-egulating these channels in neuronal membranes. Thus, drugs that can block these mediators such as NSAIDs, cytokine inhibitors (e.g. anti-TNF and anti-IL-6), suppressors of cytokines signaling (as SOCS3), or even that target specific immune cells, could be an interesting approach to treat pain. On the other hand, promoting anti-inflammatory and pro-resolution mechanisms could be also an interesting tool to control pain and inflammation.
The purpose of this Research Topic is to integrate recent advances in the field of neuro-immunology that contribute to our understanding of how cytokines and other inflammatory mediators can interact with nociceptor neurons and the impact of this interaction for health and disease. We welcome the submission of Reviews and Original Research articles covering, but not limited to, the following topics:
1. The contribution of cytokines and chemokines mediating different acute and chronic pain conditions such as inflammatory, neuropathic and articular pain (e.g. osteoarthritis, rheumatoid arthritis and gout).
2. The signaling pathways involved in neuronal activation induced by cytokines and chemokines, and how these mediators can modulate non-neuronal cells, including macrophages, neutrophils, lymphocytes, glial cells, keratinocytes, among others.
3. How these mediators participate in the development and/ or maintenance of pain. Are these mediators involved in distinct stages of pain?
4. Role in modulation of ion channels and GPCR’s at peripheral and central levels.
5. Potential new analgesics targeting these proinflammatory mediators, their receptors or cells (e.g. immunobiologicals, cytokine receptor antagonists and microglial inhibitors).
6. The involvement of pro-resolution mediators, such as resolvins, maresins and protectins in pain management.
7. Induction of anti-inflammatory pathways to control pain.
We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.
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