Mol Pain
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Complex regional pain syndrome (CRPS) is a highly enigmatic syndrome typically developing after injury or surgery to a limb. Severe pain and disability are common among those with chronic forms of this condition. Accumulating evidence suggests that CRPS may involve both autoinflammatory and autoimmune components. ⋯ More recently, autoimmune contributions have been suggested by the discovery of self-directed pain-promoting IgG and IgM antibodies in CRPS patients and model animals. Both the autoimmune and the autoinflammatory components of CRPS appear to be regulated by neuropeptide-containing peripheral nerve fibers and the sympathetic nervous system. While CRPS displays a complex neuroimmunological pathogenesis, therapeutic interventions could be designed targeting autoinflammation, autoimmunity, or the neural support for these phenomena.
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Neuropathic pain is a common chronic pain condition with mechanisms far clearly been elucidated. Mounting preclinical and clinical studies have shown neuropathic pain is highly associated with histone acetylation modification, which follows expression regulation of various pain-related molecules such as mGluR1/5, glutamate aspartate transporter, glutamate transporter-1, GAD65, Nav1.8, Kv4.3, μ-opioid receptor, brain-derived neurotrophic factor, and certain chemokines. As two types of pivotal enzymes involved in histone acetylation, histone deacetylases induce histone deacetylation to silence gene expression; in contrast, histone acetyl transferases facilitate histone acetylation to potentiate gene transcription. ⋯ In fact, numerous animal studies have suggested various histone deacetylase inhibitors, Sirt (class III histone deacetylases) activators, and histone acetyl transferases inhibitors are effective in neuropathic pain treatment via targeting specific epigenetic sites. In this review, we summarize the characteristics of the molecules and mechanisms of neuropathy-related acetylation, as well as the acetylation upregulation and blockade for neuropathic pain therapy. Finally, we will discuss the current drug advances focusing on neuropathy-related acetylation along with the underlying treatment mechanisms.
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Chronic migraine is a common chronic daily headache featured by frequent headache attacks with at least 15 headache days per month, which brings great disease burden to both the sufferers and the society. Transformed from episodic migraine, the pathophysiology of chronic migraine is not fully understood, even though several risk factors have been associated with migraine progression. ⋯ Chronic migraine is undertreated because of its poor treatment response and limited therapy options. In this article, we reviewed the latest data to outline the clinical feature, pathophysiological mechanism, and management of chronic migraine, in the expectation to provide direction for future research and finally to take good care of chronic migraine patients.
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Primary sensory neurons in the dorsal root ganglia and trigeminal ganglia are responsible for sensing mechanical and thermal stimuli, as well as detecting tissue damage. These neurons express ion channels that respond to thermal, mechanical, or chemical cues, conduct action potentials, and mediate transmitter release. These neurons also express a large number of G-protein coupled receptors, which are major transducers for extracellular signaling molecules, and their activation usually modulates the primary transduction pathways. ⋯ On the other hand, receptors that couple to Gi/o proteins, such as opioid or GABAB receptors, are generally inhibitory. Their activation counteracts the effect of Gs-stimulation by inhibiting adenylate cyclase, as well as exerts effects on ion channels, usually resulting in decreased excitability. This review will summarize knowledge on Gi-coupled receptors in sensory neurons, focusing on their roles in ion channel regulation and discuss their potential as targets for analgesic and antipruritic medications.
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Complex regional pain syndrome is an extremely painful condition that develops after trauma to a limb. Complex regional pain syndrome exhibits autoimmune features in part mediated by autoantibodies against muscarinic-2 acetylcholine (M2) receptor. ⋯ As both complex regional pain syndrome and the proalgesic myelin basic protein activity are prevalent in females, this myelin basic protein/M2 homology presents an inviting hypothesis explaining the mechanisms of autoimmune pathogenesis and sexual dimorphism that underlies vulnerability toward developing complex regional pain syndrome and other pain states with neuropathic features. This hypothesis may aid in the development of novel diagnostic and therapeutic strategies to chronic pain.