Ali Akbar OWJI, Kaveh RAHIMI, Javad SAJEDIANFARD

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

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

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Gebhart GF. Descending modulation of pain. Neuroscience & Biobehavioral Reviews 2004;27:729-37.
Ossipov MH, Dussor GO, Porreca F. Central modulation of pain. J Clin Invest 2010;120:3779-87. García-Ramírez DL, Calvo JR, Hochman S, Quevedo JN. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord. PLoS One 2014;9:e89999.
Kwiat GC, Basbaum AI. Organization of tyrosine hydroxylase- and serotonin-immunoreactive brainstem neurons with axon collaterals to the periaqueductal gray and the spinal cord in the rat. Brain Res 1990;528:83-94.
Fischer JA, Born W. Novel peptides from the calcitonin gene: expression, receptors and biological function. Peptides 1985;6(Suppl 3):265-71.
Born W, Fischer JA. Calcitonin Gene Products: Molecular Biology, Chemistry, and Actions. Physiology and Pharmacology of Bone. Berlin, Heidelberg: Springer Berlin Heidelberg 1993:569-616.
Murakoshi M, Ikeda R, Horiuchi T, Nakayama K, Kurotani R, Osamura RY. Immunoreactive pit-1 protein in hyperplastic pars intermedia induced by calcitonin of the rat pituitary gland. Endocr J 2000;47:13-20.
Gorn AH, Lin HY, Yamin M, Auron PE, Flannery MR, Tapp DR, et al. Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line. J Clin Invest 1992;90:1726-35.
Kuestner RE, Elrod RD, Grant FJ, Hagen FS, Kuijper JL, Matthewes SL, et al. Cloning and characterization of an abundant subtype of the human calcitonin receptor. Mol Pharmacol 1994;46:246-55.
Sexton PM, McKenzie JS, Mason RT, Moseley JM, Martin TJ, Mendelsohn FA. Localization of binding sites for calcitonin gene-related peptide in rat brain by in vitro autoradiography. Neuroscience 1986;19:1235-45.
Kruger L, Mantyh PW, Sternini C, Brecha NC, Mantyh CR. Calcitonin gene-related peptide (CGRP) in the rat central nervous system: patterns of immunoreactivity and receptor binding sites. Brain Res 1988;463:223-44.
Sexton PM, McKenzie JS, Mendelsohn FA. Evidence for a new subclass of calcitonin/ calcitonin gene-related peptide binding site in rat brain. Neurochem Int 1988;12:323-35.
Sexton PM. Central nervous system binding sites for calcitonin and calcitonin gene-related peptide. Mol Neurobiol 1991;5:251-73.
Goltzman D, Tannenbaum GS. Induction of hypocalcemia by intracerebroventricular injection of calcitonin: evidence for control of blood calcium by the nervous system. Brain Res 1987;416:1-6.
Li Z, Gao Z, Li S, Zhang Y, Xing L, Zhang L, et al. Microinjection of calcitonin in midbrain periaqueductal gray attenuates hyperalgesia in a chronic constriction injury rat model. Iran J Basic Med Sci 2015;18:72-9.
Pecile A, Guidobono F, Netti C, Sibilia V, Biella G, Braga PC. Calcitonin gene-related peptide: antinociceptive activity in rats, comparison with calcitonin. Regul Pept 1987;18:189-99.
Candeletti S, Ferri S. Antinociceptive profile of intracerebroventricular salmon calcitonin and calcitonin gene-related peptide in the mouse formalin test. Neuropeptides 1990;17:93-8.
Paxinos GCW. The Rat Brain in Stereotaxic Coordinates. Sydney: Academic Press 2006.
Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977;4:161-74.
Coderre TJ, Fundytus ME, McKenna JE, Dalal S, Melzack R. The formalin test: a validation of the weighted-scores method of behavioural pain rating. Pain 1993;54:43-50.
Rahimi K, Sajedianfard J, Owji AA. The effect of intracerebroventricular injection of CGRP on pain behavioral responses and monoamines concentrations in the periaqueductal gray area in rat. Iran J Basic Med Sci 2018;21:395-9.
Kilinc E, Dagistan Y, Kukner A, Yilmaz B, Agus S, Soyler G, et al. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats. Clin Exp Pharmacol Physiol 2018;45:536-46.
Terashima Y, Takebayashi T, Jimbo S, Ogon I, Sato T, Ichise N, et al. Analgesic effects of calcitonin on radicular pain in male rats. J Pain Res 2019;12:223-30.
Gou Y, Tian F, Kong Q, Chen T, Li H, Lv Q, et al. Salmon Calcitonin Attenuates Degenerative Changes in Cartilage and Subchondral Bone in Lumbar Facet Joint in an Experimental Rat Model. Med Sci Monit 2018;24:2849-57.
Ito A, Takeda M, Yoshimura T, Komatsu T, Ohno T, Kuriyama H, et al. Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors. Mol Pain 2012;8:42.
Clementi G, Prato A, Conforto G, Scapagnini U. Role of serotonin in the analgesic activity of calcitonin. Eur J Pharmacol 1984;98:449-51.
Nakhla AM, Nandi Majumdar AP. Calcitonin-mediated changes in plasma tryptophan and brain 5-hydroxytryptamine and acetylcholinesterase activity in rats. Biochem J 1978;170:445-8.
Bobinski F, Ferreira TAA, Córdova MM, Dombrowski PA, da Cunha C, Santo CCDE, et al. Role of brainstem serotonin in analgesia produced by low-intensity exercise on neuropathic pain after sciatic nerve injury in mice. Pain 2015;156:2595-606.
Ito A, Yoshimura M. Mechanisms of the analgesic effect of calcitonin on chronic pain by alteration of receptor or channel expression. Mol Pain 2017;13:1744806917720316.
Flores JA, El Banoua F, Galán-Rodríguez B, Fernandez-Espejo E. Opiate anti-nociception is attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not D2) dopamine receptors. Pain 2004;110:205-14.
Sajedianfard J, Khatami S, Semnanian S, Naghdi N, Jorjani M. In vivo measurement of noradrenaline in the locus coeruleus of rats during the formalin test: a microdialysis study. Eur J Pharmacol 2005;512:153-6.
Fritschy JM, Grzanna R. Demonstration of two separate descending noradrenergic pathways to the rat spinal cord: evidence for an intragriseal trajectory of locus coeruleus axons in the superficial layers of the dorsal horn. J Comp Neurol 1990;291:553-82.
Bartsch T, Knight YE, Goadsby PJ. Activation of 5-HT(1B/1D) receptor in the periaqueductal gray inhibits nociception. Ann Neurol 2004;56:371-81.
Estrada VB, Matsubara NK, Gomes MV, Corrêa FM, Pelosi GG. Noradrenaline microinjected into the dorsal periaqueductal gray matter causes anxiolytic-like effects in rats tested in the elevated T-maze. Life Sci 2016;152:94-8. Huang CL, Sun L, Moonga BS, Zaidi M. Molecular physiology and pharmacology of calcitonin. Cell Mol Biol (Noisy-le-grand) 2006;52:33-43.
Chesnut CH, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2000;109:267-76.
Chesnut CH, Azria M, Silverman S, Engelhardt M, Olson M, Mindeholm L. Salmon calcitonin: a review of current and future therapeutic indications. Osteoporos Int 2008;19:479-91.
Haddadi K, Asadian L, Isazade A. Effects of Nasal Calcitonin vs. Oral Gabapentin on Pain and Symptoms of Lumbar Spinal Stenosis: A Clinical Trial Study. Clin Med Insights Arthritis Musculoskelet Disord 2016;9:133-8.
Karponis A, Rizou S, Pallis D, Zafeiris CP, Georgiou DF, Galanos A, et al. Analgesic effect of nasal salmon calcitonin during the early post-fracture period of the distal radius fracture. J Musculoskelet Neuronal Interact 2015;15:186-9.
Henriksen K, Byrjalsen I, Andersen JR, Bihlet AR, Russo LA, Alexandersen P, et al. A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. Bone 2016;91:122-9.
Karsdal MA, Byrjalsen I, Alexandersen P, Bihlet A, Andersen JR, Riis BJ, et al. Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials. Osteoarthritis Cartilage 2015;23:532-43.
Knopp-Sihota JA, Newburn-Cook CV, Homik J, Cummings GG, Voaklander D. Calcitonin for treating acute and chronic pain of recent and remote osteoporotic vertebral compression fractures: a systematic review and meta-analysis. Osteoporos Int 2012;23:17-38.