Neuropathic pain; what we know and what we should do about it

Abstract

Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve injury promotes Schwann cell activation and invasion of immunocompetent cells into the site of injury, spinal cord and higher sensory structures such as thalamus and cingulate and sensory cortices. Various cytokines, chemokines, growth factors, monoamines and neuropeptides effect two-way signalling between neurons, glia and immune cells. This promotes sustained hyperexcitability and spontaneous activity in primary afferents that is crucial for onset and persistence of pain as well as misprocessing of sensory information in the spinal cord and supraspinal structures. Much of the current understanding of pain aetiology and identification of drug targets derives from studies of the consequences of peripheral nerve injury in rodent models. Although a vast amount of information has been forthcoming, the translation of this information into the clinical arena has been minimal. Few, if any, major therapeutic approaches have appeared since the mid 1990's. This may reflect failure to recognise differences in pain processing in males vs. females, differences in cellular responses to different types of injury and differences in pain processing in humans vs. animals. Basic science and clinical approaches which seek to bridge this knowledge gap include better assessment of pain in animal models, use of pain models which better emulate human disease, and stratification of human pain phenotypes according to quantitative assessment of signs and symptoms of disease. This can lead to more personalized and effective treatments for individual patients. Significance statement: There is an urgent need to find new treatments for neuropathic pain. Although classical animal models have revealed essential features of pain aetiology such as peripheral and central sensitization and some of the molecular and cellular mechanisms involved, they do not adequately model the multiplicity of disease states or injuries that may bring forth neuropathic pain in the clinic. This review seeks to integrate information from the multiplicity of disciplines that seek to understand neuropathic pain; including immunology, cell biology, electrophysiology and biophysics, anatomy, cell biology, neurology, molecular biology, pharmacology and behavioral science. Beyond this, it underlines ongoing refinements in basic science and clinical practice that will engender improved approaches to pain management.

Neural ensembles that encode affective mechanical and heat pain in mouse spinal cord

“…Neuropathic pain resulting from peripheral nerve injury leads to colony-stimulating facto-1 (Csf1) released from primary afferents that drives microglia activation and a secondary neuroinflammation in the spinal cord 51 . Microglial cells have an important role in initiating and maintaining pain and inflammation 49,[79][80][81] . Our results concur with these studies as we find a marked transition of resting state (M0) into activated (M1) microglia.…”

The effect of perineural injection therapy on neuropathic pain: a retrospective study

“…Among the pain that occurs in the facial area managed in the dental field, neuropathic pain, which is classified as incurable, is included. Neuropathic pain refers to chronic pain that persists due to nerve damage or abnormal nerve function, and representative examples include post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), peripheral neuropathy (PN), failed spine surgery syndrome, and pain due to cancer [ 1 ]. Unlike tissue damage, such as muscle or ligament injury, which is commonly experienced when we twist our back, neuropathic pain, in which the nerve itself is damaged, becomes chronic and is prone to hypersensitivity, making mild pain feel more severe or even normal stimulation painful.…”