Neuropathic pain arises as a direct consequence of a lesion or disease of the somatosensory system. A hallmark of neuropathic pain is the proliferation, morphological changes and activation of microglia in the spinal dorsal horn. Salter and cols discovered a form of neuropathic pain that is independent of microglia. Nucleus pulposus secrete soluble factor which recruit macrophages into the sciatic nerve where they release BDNF which induce pain hypersensitivity. These findings help to explain the limited success of microglial inhibitors on neuropathic pain in human clinical trials.

Parkinson’s Disease (PD) has traditionally been considered a neurodegenerative disease with motor involvement associated with the accumulation and misfolding of the protein alpha-synuclein (aSyn). However, non-motor symptoms such as thermal and mechanical sensory dysfunction, as well as a considerable decrease in intraepidermal nerve fibers, are becoming more important in these patients; It remains unclear how aSyn misfolding could affect these symptoms.

It is well known that chronic pain states in humans may generate complex emotional imbalances. Many studies have shown that chronic pain indeed causes negative emotions and common pathologies, such as anxiety and depression. However, how chronic pain produces anxiety and depression at the brain level is unknown.

According to the authors, the enzyme PDI (Protein Dithiol Isomerase) would be a novel participant in chronic pain regulation, activating TRPV1 allosterically (ligand-independent), which would lead to heat hyperalgesia (increase pain in response to noxious heat).

In this study, authors demonstrated that GPR151 is highly expressed in dorsal root ganglion neurons (DRG). This receptor, coupled with the P2X3 ionic channels, modulates CSF1-induced microglial activation, which is essential for the initiation and maintenance of neuropathic pain. This data portray GPR151 and P2X3 as a promising therapeutic targets for this condition.

A huge number of epidemiological studies demonstrate that chronic pain conditions are more common in women than in men. Women are also at a greater risk for developing common chronic pain conditions including migraines, low back pain, fibromyalgia, and irritable bowel syndrome.