Central Neuropathic Mechanisms in Pain Signaling Pathways: Current Evidence and Recommendations

Abstract

Purpose This is a comprehensive review of the current literature on central neuropathic pain mechanisms that is secondary to spinal cord injury. It reviews recent and seminal findings on the pathophysiology, diagnosis, and treatment and compares treatment options and recommendations. Recent Findings Neuropathic pain (NP) is a common complication of spinal cord injury (SCI). Chronicity of NP is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve–glia cross talk have also been implicated. Conventional treatment is medical and has had limited success. Recent studies have made headway in identifying novel biomarkers, including microRNA and psychosocial attributes that can predict progress from SCI to chronic NP (CNP). Recent advances have provided evidence of efficacy for two promising drugs. Baclofen was able to provide good, long-lasting pain relief. Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase (CPK) elevations, and further studies are required to define its safety profile. Non-medical interventions include brain sensitization and biofeedback techniques. These methods have recently had encouraging results, albeit preliminary. Case reports of non-conventional techniques, such as hypnosis, were also reported. Summary CNP is a common complication of SCI and is a prevalent disorder with significant morbidity and disability. Conventional medical treatment is limited in efficacy. Recent studies identified baclofen and ziconotide as possible new therapies, alongside non-medical interventions. Further research into the pathophysiology is required to identify further therapy candidates. A multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve therapeutic effects in this difficult to treat syndrome.

Pain and Neuropathic Pain in Rheumatic Diseases

“…Throughout these studies, we found that LPA plays a key role in pain memory, and that LPA 1 receptor-and LPA 3 receptor-antagonists could reverse the established pain, and thereby cure the disease source of pain [28]. Chronicity of neuropathic pain is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve-glia cross talk have also been implicated [29]. Further development in understanding of neuropathic pain mechanisms will help to identify new possibilities for pain treatment (▶ fig.…”

“…Peripheral Fibers Increase of peripheral sensitivity Expression of endogenous ligands and receptors on injured nerve target Increase of NF-kB pathway activity Promote the production of leukotriene ▶fig. 1 Pathophysiology of neuropathic pain [21][22][23][24][25][26][27][28][29]. lysophosphatidic acid (LPA), gamma-aminobutyric acid (GABAergic) interneurons, nuclear factor 'kappa-light-chain-enhancer' (NF-κB).…”

“…Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase elevations, and further studies are required to define its safety profile [29].…”

“…These methods revealed recently encouraging results. Case reports of non-conventional techniques, such as hypnosis, were also reported [29]. In addition, it has been suggested that the importance of pain rehabilitation techniques will increase over time and that these measurements will play a larger role in the management of neuropathic pain.…”

A Review of the Recent Findings in Minimally Invasive Treatment Options for the Management of Occipital Neuralgia

“…No longer term studies with larger sample sizes have been conducted to further support the use of infliximab for the treatment of ON. There have been studies examining the best target for therapeutic management, and a multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve success in this difficult to treat syndrome [24].…”