Neuropathic Pain: Central vs. Peripheral Mechanisms

Abstract

Recent preclinical studies in pNP support and provide key details concerning the role of multiple mechanisms leading to fiber hyperexcitability and sustained electrical discharge to the CNS. In studies regarding central mechanisms, new preclinical evidence includes the mapping of novel inhibitory circuitry and identification of the molecular basis of microglia-neuron crosstalk. Recent clinical evidence demonstrates the essential role of peripheral mechanisms, mostly via studies that block the initially damaged peripheral circuitry. Clinical central mechanism studies use imaging to identify potentially self-sustaining infra-slow CNS oscillatory activity that may be unique to pNP patients. While new preclinical evidence supports and expands upon the key role of central mechanisms in neuropathic pain, clinical evidence for an autonomous central mechanism remains relatively limited. Recent findings from both preclinical and clinical studies recapitulate the critical contribution of peripheral input to maintenance of neuropathic pain. Further clinical investigations on the possibility of standalone central contributions to pNP may be assisted by a reconsideration of the agreed terms or criteria for diagnosing the presence of central sensitization in humans.

Domains of Chronic Low Back Pain and Assessing Treatment Effectiveness: A Clinical Perspective

“…In the case of an increased wind‐up mechanism, the temporal pain response is increased from the first to last repetition . This process within the spinal cord may lead to dynamic changes in second‐order spinal neurons (eg, dorsal horn) that could be important for the development and maintenance of central sensitization in CLBP . It is also believed that central sensitization provides an overarching framework to better understand the transition of large‐scale brain network activity in acute to chronic pain .…”

“…24 This process within the spinal cord may lead to dynamic changes in second-order spinal neurons (eg, dorsal horn) that could be important for the development and maintenance of central sensitization in CLBP. 25 It is also believed that central sensitization provides an overarching framework to better understand the transition of large-scale brain network activity in acute to chronic pain. 26 In acute or experimental pain conditions, the brain networks activated are those mostly involved in the processing of the sensory-discriminative nature of pain (eg, somatosensory cortex), whereas in chronic pain, the activity shifts to the brain networks related to emotional processing (eg, prefrontal cortex).…”

Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats

“…The mechanisms of NP are involved in both peripheral and central sensitization, but the precise mechanism is still unclear (Meacham et al, 2017). In recent years, spinal astrocytes have been reported to play a significant role in the induction and maintenance of NP (Mika et al, 2013).…”

Hyperpolarization‐activated channels shape temporal patterns of ectopic spontaneous discharge in C‐nociceptors after peripheral nerve injury

“…Spontaneous pain, the main symptom reported by patients with peripheral neuropathies (Truini et al, 2013;Vollert et al, 2017), seems to originate and prevail through aberrant spontaneous discharges fired by peripheral afferents (Baron et al, 2013;Meacham et al, 2017). The ectopic reorganization of different Nav and Kv channels renders hyperexcitable membranes leading to abnormal firing (Campbell and Meyer, 2006;Devor, 2006).…”