Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases.
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.
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Lila
0000-0002-9354-8037
L
Carniglia
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Delia
0000-0003-2253-1710
D
Ramírez
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Daniela
0000-0003-2361-1165
D
Durand
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Julieta
0000-0003-0002-7134
J
Saba
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Juan
0000-0003-3817-0489
J
Turati
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Carla
0000-0002-0889-0293
C
Caruso
IFEC-CONICET, Depto. Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Teresa N
0000-0001-8701-5771
TN
Scimonelli
INBIOMED (Instituto de Investigaciones Biomédicas), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina.
Mercedes
0000-0001-9916-3712
M
Lasaga
D053607:Adrenomedullin / Q000378:metabolism; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators; D020738:Leptin / Q000378:metabolism; D008262:Macrophage Activation; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D054439:Ghrelin; D018836:Inflammation Mediators; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D015320:Tachykinins; C099323:cortistatin; D053607:Adrenomedullin; D014660:Vasoactive Intestinal Peptide; D011333:Pro-Opiomelanocortin; D015740:Calcitonin Gene-Related Peptide