Neuraxial Cytokines in Pain States

Abstract

A high-intensity potentially tissue-injuring stimulus generates a homotopic response to escape the stimulus and is associated with an affective phenotype considered to represent pain. In the face of tissue or nerve injury, the afferent encoding systems display robust changes in the input-output function, leading to an ongoing sensation reported as painful and sensitization of the nociceptors such that an enhanced pain state is reported for a given somatic or visceral stimulus. Our understanding of the mechanisms underlying this non-linear processing of nociceptive stimuli has led to our appreciation of the role played by the functional interactions of neural and immune signaling systems in pain phenotypes. In pathological states, neural systems interact with the immune system through the actions of a variety of soluble mediators, including cytokines. Cytokines are recognized as important mediators of inflammatory and neuropathic pain, supporting system sensitization and the development of a persistent pathologic pain. Cytokines can induce a facilitation of nociceptive processing at all levels of the neuraxis including supraspinal centers where nociceptive input evokes an affective component of the pain state. We review here several key proinflammatory and anti-inflammatory cytokines/chemokines and explore their underlying actions at four levels of neuronal organization: (1) peripheral nociceptor termini; (2) dorsal root ganglia; (3) spinal cord; and (4) supraspinal areas. Thus, current thinking suggests that cytokines by this action throughout the neuraxis play key roles in the induction of pain and the maintenance of the facilitated states of pain behavior generated by tissue injury/inflammation and nerve injury.

Metabolomic analysis coupled with extreme phenotype sampling identified that lysophosphatidylcholines are associated with multisite musculoskeletal pain

“…We also observed younger age was associated with MSMP, which could be due to higher physical workload and mental stress before retirement in the MSMP group, 24 , 66 supporting what Neupane et al 44 suggested that MSMP in midlife often persisted to old age in a MSMP trajectory study over 28 years. Cytokines are believed to play a role in pain modulation 19 , 42 , 64 ; however, we did not observe any association between MSMP and plasma levels of MIF, IL-6, IL-1β, or TNF-α. Although further studies are needed to confirm this, our findings were consistent with others.…”

Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain

“…In the first week after nerve injury, macrophages flow into DRG [34]. Currently, it is known that in addition to resident and recruited immune cells present throughout the neuraxis, cytokines are released from neuronal cells [35]. Thus, cytokines compose a communication network between immune and neuronal cells.…”

“…Thus, cytokines compose a communication network between immune and neuronal cells. Interleukins (IL-1beta, IL-18 and IL-6) are recognized as the first pronociceptive cytokines in neuropathy [ 35 ] and are known to be strongly activated upon neural damage in the CNS and PNS [ 35 – 39 ]. In our previous studies, we showed that minocycline administered ip has an analgesic effect in parallel with diminished immunological factors, such as IL-1beta and IL-18 in DRG [ 40 , 41 ].…”

Metamizol como inmunomodulador en el dolor neuropático

“…Los mecanismos inmunes cada vez están teniendo más protagonismo en la fisiopatología del dolor neuropático, y diversas citoquinas y quimioquinas parecen jugar un papel importante a nivel del sistema nervioso periférico y central por su efecto pronociceptivo (8). Sabemos que en el ganglio de la raíz dorsal, donde se encuentra en núcleo celular, tiene lugar una gran actividad metabólica que rige la nocicepción.…”