The Role of Neuro-Immune Interactions in Chronic Pain: Implications for Clinical Practice

Abstract

Chronic pain remains a public health problem and contributes to the ongoing opioid epidemic. Current pain management therapies still leave many patients with poorly controlled pain, thus new or improved treatments are desperately needed. One major challenge in pain research is the translation of preclinical findings into effective clinical practice. The local neuroimmune interface plays an important role in the initiation and maintenance of chronic pain and is therefore a promising target for novel therapeutic development. Neurons interface with immune and immunocompetent cells in many distinct microenvironments along the nociceptive circuitry. The local neuroimmune interface can modulate the activity and property of the neurons to affect peripheral and central sensitization. In this review, we highlight a specific subset of many neuroimmune interfaces. In the central nervous system, we examine the interface between neurons and microglia, astrocytes, and T lymphocytes. In the periphery, we profile the interface between neurons in the dorsal root ganglion with T lymphocytes, satellite glial cells, and macrophages. To bridge the gap between preclinical research and clinical practice, we review the preclinical studies of each neuroimmune interface, discuss current clinical treatments in pain medicine that may exert its action at the neuroimmune interface, and highlight opportunities for future clinical research efforts.

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

“…Third, this type of contact needs to be confirmed further in tissue sections/co-culture of neurons/glial cell and immune cells by using EM and immuno-EM as described in a few previous studies ( 175 , 176 ). Once enough anatomical/morphological evidence of nerve-immune cell interaction has been obtained, further molecular/physiological/functional studies should be conducted to reveal the molecular mechanism of this type of local neuroimmune interaction ( 20 , 177 – 179 ).…”

The mechanisms and management of persistent postsurgical pain

“…During surgery, nerves are at risk of injury from partial or complete transection, stretching, crushing, electrical damage, entrapment, or compression ( 35 , 74 , 76 – 78 ). Nerve injury is associated with many molecular and cellular changes comprizing neuroimmune interactions ( 79 , 80 ). It is entirely conceivable that duration of surgery, associated with sustained peripheral injury, could trigger changes in the central nervous system (CNS).…”

Natural polyphenolic coffee extract administration relieves chronic nociplastic pain in a reserpine‐induced fibromyalgia‐like female mouse model

“…That is, a pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain (Treede et al., 2019 ). The underlying mechanisms of FM remain unknown, but recent studies suggest that neuroinflammation processes may play a pivotal role in FM pathogenesis (Correa‐Rodríguez et al., 2020 ; Coskun Benlidayi, 2019 ), in which microglia cells may be involved by releasing pain‐inducing proinflammatory factors (Coskun Benlidayi, 2019 ; Su et al., 2022 ). Despite the increasing knowledge about potential mechanisms, no suitable pharmacological strategies have been developed yet for FM treatment (Coskun Benlidayi, 2019 ).…”