The Effects of Salmon Calcitonin on the Concentrations of Periaqueductal Gray Monoamines in the Formalin Test

Abstract

Background: The receptors of salmon calcitonin, located on certain areas of the brain such as the periaqueductal gray matter, are responsible for pain modulation. Aims: The effects of intracerebroventricular injection of salmon calcitonin on the behavioral response to pain and on the levels of monoamines in the periaqueductal gray were explored using a biphasic animal model of pain. Study Design: Animal experiment. Methods: A total of 45 male rats were divided into four groups (n=6). Salmon calcitonin was injected into the lateral ventricle of the brain (1.5 nmol, with a volume of 5 μL). After 20 min, 2.5% formalin was subcutaneously injected into the right leg claw, and pain behavior was recorded on a numerical basis. At the time of the formalin test, the periaqueductal gray area was microdialized. High-performance liquid chromatography method was used to gauge the levels of monoamines and their metabolites. Results: Intracerebroventricular injections of salmon calcitonin resulted in pain reduction in the formalin test (p<0.05). The dialysate concentrations of serotonin, dopamine, norepinephrine, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic, and 4-hydroxy-3-methoxyphenylglycol increased in the periaqueductal gray area in different phases of the formalin pain test (p<0.05). Conclusion: Salmon calcitonin reduced pain by increasing the concentrations of monoamines and the metabolites derived from them in the periaqueductal gray area.

Calcitonin Gene-Related Peptide and Calcitonin mRNA Expression in Periaqueductal Gray Area in the Formalin Test in Rats

“…In the current study, the ICV injection of CGRP peptide reduced pain in the formalin test. Various studies have also reported the analgesic effects of CGRP (10,(26)(27)(28). We found that following the ICV injection of CGRP, rCT mRNA expression increased in the PAG area.…”

“…In addition, the CGRP mRNA is observed in the dura mater, pituitary, hypothalamus, PAG, hippocampus, and cingulate gyrus (29). Inflammogenic substances, such as formalin, directly activate the transient potential receptors of TRPA1 and TRPV1 in the dorsal root ganglia and stimulate CGRP synthesis (27,28). The presence of CGRP causes its synthesis in the neurons (29).…”

Beyond CGRP: The calcitonin peptide family as targets for migraine and pain

“…Rodent models have been used to explore the analgesic properties of sCT. For example, pre-administration or co-administration of sCT reduced threshold in the nociceptive hot plate test and reduced the frequency of pain-related behaviours, such as licking (Clementi et al, 1984;Hamada et al, 2018;Rahimi et al, 2019;Sibilia et al, 2000;Yeh et al, 2016). The proposed mechanism is attenuation of central sensitisation or the modulation of pain via 5-HT mediated pathways.…”

“…Interestingly, sCT administration is also associated with lower neuronal activation in the spinal cord and STN, measured as c-fos expression, and increased expression of 5-HT and other monoamines in the periaqueductal grey (Khoshdel et al, 2014;Kilinc et al, 2018;Rahimi et al, 2019;Yeh et al, 2016). In the brain, sCT is reported to decrease neural sodium-dependent 5-HT transporter activity, thereby potentiating the actions of 5-HT in the synapse, resulting in increased 5-HT 1 receptor activity (Yeh et al, 2016).…”

The analgesic effects of insulin and its disorders in streptozotocin‐induced short‐term diabetes

“…Most previous investigations of neuropathic pain have focused on peripheral mechanisms of sensitization but recent concepts agree that central sensitization is also involved in neuropathic pain (Zimmermann, 2001). The periaqueductal gray (PAG) is a midbrain structure involved in the descending control of pain (Millan, 2002; Rahimi et al., 2019). Some glutamatergic neurons project from the PAG to the rostral ventromedial medulla, which suppresses pain signals (Heinricher et al., 2009).…”