Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Abstract

Microglial cells are responsible for immune surveillance within the CNS. They respond to noxious stimuli by releasing inflammatory mediators and mounting an effective inflammatory response. This is followed by release of anti-inflammatory mediators and resolution of the inflammatory response. Alterations to this delicate process may lead to tissue damage, neuroinflammation, and neurodegeneration. Chronic pain, such as inflammatory or neuropathic pain, is accompanied by neuroimmune activation, and the role of glial cells in the initiation and maintenance of chronic pain has been the subject of increasing research over the last two decades. Neuropeptides are small amino acidic molecules with the ability to regulate neuronal activity and thereby affect various functions such as thermoregulation, reproductive behavior, food and water intake, and circadian rhythms. Neuropeptides can also affect inflammatory responses and pain sensitivity by modulating the activity of glial cells. The last decade has witnessed growing interest in the study of microglial activation and its modulation by neuropeptides in the hope of developing new therapeutics for treating neurodegenerative diseases and chronic pain. This review summarizes the current literature on the way in which several neuropeptides modulate microglial activity and response to tissue damage and how this modulation may affect pain sensitivity.

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors

“…In addition, leptin expression can be regulated by cytokines. (Carniglia et al, 2017) While no studies were found on associations between leptin and CIPN, in a rat model of chronic constriction injury, administration of a leptin antagonist prevented the development of injuryinduced mechanical allodynia and thermal hyperalgesia. (Lim et al, 2009) In a mouse model of partial sciatic nerve ligation, (Maeda et al, 2009) leptin production was induced in the adipocytes that were present in the epineurium of the injured nerve and leptin was necessary for tactile allodynia associated with the ligation.…”

Influence of bisfenol A on chemical coding of the nerve fibers of the cardiac apex in the domestic pig

“…Spośród kilkudziesięciu neuroprzekaźników i/lub neuromodulatorów opisanych dotychczas na terenie układu nerwowego wybrano: neuropeptyd Y (NPY), pęcherzykowy transporter acetylocholiny (VAChT), hydroksylazę tyrozynową (TH), substancję P (SP), transkrypt regulowany kokainą i amfetaminą (CART) oraz peptyd kodowany genem kalcytoniny (CGRP). Wiadomo, iż substancje te na terenie układu nerwowego pełnią istotną rolę (6,11), a ponadto większość z nich uczestniczy również w regulacji aktywności mięśnia sercowego, dlatego też wyniki otrzymane w niniejszym doświadczeniu mogą w znacznym stopniu poszerzyć wiedzę na temat mechanizmów działania bisfenolu A na żywy organizm.…”

CGRP and Brain Functioning: Cautions for Migraine Treatment

“…This effect is stimulus‐ and tissue‐specific. CGRP is anti‐inflammatory when microglia are activated through toll‐like receptors [innate immunity, as in the MS model] but proinflammatory in pain pathways when microglia are activated by nociceptive signaling …”

“…That is, CGRP may contribute to classical inflammation in pain processing regions and may attenuate such inflammation elsewhere in the brain. CGRP has also been implicated in signaling cascades in neurons, microglia, and astrocytes underlying tolerance to morphine …”