Anti-Hyperalgesic Effects of Calcitonin on Neuropathic Pain Interacting with its Peripheral Receptors

Ito, Akitoshi; Takeda, Masami; Yoshimura, Takeshi; Komatsu, Takayuki; Ohno, Takeshi; Kuriyama, Hiroshi; Matsuda, Akio; Yoshimura, Michihiro

doi:10.1186/1744-8069-8-42

Cited by 37 publications

(40 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was previously demonstrated in many prospective studies that subcutaneous or intranasal application of SC exhibited analgesic effects . It was shown that calcitonin provided anti‐hyperalgesic effect on pain behaviours in chronic constriction injury‐induced hyperalgaesia in rats . In a clinical prospective study, 200 IU of intranasal SC was administered to postmenopausal women with distal radius fracture daily for 3 months following the fracture formation.…”

Section: Discussionmentioning

confidence: 99%

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

Kılınç

Dağıstan

Kükner

et al. 2018

Clin Exp Pharma Physio

View full text Add to dashboard Cite

The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. Rats were intraperitoneally administered saline, GTN (10 mg/kg), vehicle, saline + GTN, SC (50 μg/kg) + GTN, and SC alone. Also, ex vivo meningeal preparations were applied topically 100 μmol/L GTN, 50 μmol/L SC, and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma, trigeminal neurons and superfusates were measured using enzyme-immunoassays. Dural mast cells were stained with toluidine blue. c-fos neuronal activity in trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical staining. The results showed that GTN triggered the increase in CGRP levels in plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise, GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural mast cell degranulation, but similar effects were not seen in ex vivo experiments. Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief.

show abstract

Section: Discussionmentioning

confidence: 99%

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

Kılınç

Dağıstan

Kükner

et al. 2018

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…It has been reported that administration of elcatonin ameliorates enhanced arterial contractility 24) and repeated administration of elcatonin is attributable to normalization of the sodium channels expression in chronic constriction injury neuropathic rats. 25) Thus, restoration of the expression level of the sodium channels may be one of the mechanisms of the anti-allodynic effects of calcitonins.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, calcitonin receptors have been reported to express in peripheral nerve tissues such as Schwann cells, not in dorsal root ganglion cells. 25) Therefore, we assume that neurotrophic factors derived from peripheral nerve tissues by stimulation of calcitonin receptors could modify the gene expression in dorsal root ganglion cells and regional blood flow. Further investigation is still required to determine the exact mechanisms by which calcitonins take effect, including modulation of these thermosensitive channels and Na + channels, and regional blood flow, through the activation of calcitonin receptors.…”

Section: Discussionmentioning

confidence: 99%

Salmon Calcitonin Reduces Oxaliplatin-Induced Cold and Mechanical Allodynia in Rats

Aoki

Mori

Nakahara

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Oxaliplatin is commonly used anti-cancer drugs, but it frequently causes peripheral neuropathic pain. Recently, we reported that elcatonin, a synthetic analog of eel calcitonin, attenuated the oxaliplatin-and paclitaxel-induced cold and mechanical allodynia in rats. In the present study, we determined whether salmon calcitonin also had anti-allodynic effects on oxaliplatin-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, intraperitoneally (i.p.)). Oxaliplatin resulted in cold and mechanical allodynia. We assessed the anti-allodynic effects of subcutaneously administered salmon calcitonin (20 U/ kg/d) by cold stimulation (8°C) directly to the hind paw of the rats and by using the von Frey test. Salmon calcitonin almost completely reversed the effects of both cold and mechanical allodynia. These results suggest that salmon calcitonin is also useful for treatment of oxaliplatin-induced neuropathy clinically.Key words oxaliplatin; salmon calcitonin; peripheral neuropathy Platinum-based drugs 1) is commonly administered to patients with various types of cancers. Oxaliplatin is commonly used for the treatment of advanced metastatic colorectal cancer, 2) and is known to induce a specific acute and chronic form of neuropathy. In particular, cold allodynia of the hands, feet, perioral region, and throat appears soon after its administration. Indeed, neurotoxicity as a result of oxaliplatin is often the reason for treatment discontinuation, dose reduction, or hospitalization, rather than tumor progression. 3)Calcitonin is a hormone that occurs naturally in the human body, and inhibits bone resorption through the direct inhibition of osteoclastic activity.4) It is effective against severe pain associated with vertebral fracture, 5,6) postosteoporotic fracture, 5,7) Paget's disease, 7) and lumbago. 8) In addition, calcitonin has been reported to relieve pain that is not related to osteoporosis, such as that of diabetic neuropathy, 9) reflex sympathetic dystrophy, 10,11) migraine, 12) and formalin-induced hyperalgesia and allodynia.13) Recently, we reported that elcatonin, a synthetic analog of eel calcitonin, attenuated oxaliplatin-and paclitaxel-induced cold and mechanical allodynia in rats. 14) Although blockade of the cellular signaling related to transient receptor potential ankyrin-1 (TRPA1) and melastatin-8 (TRPM8) is involved in the anti-allodynic action of elcatonin, it has been still unclear whether stimulation of calcitonin receptors is involved in the underlying mechanisms. 14)Salmon calcitonin is similar to human calcitonin hormone in many ways, and more potent than human calcitonin. Therefore, salmon calcitonin is also widely used to treat postmenopausal osteoporosis. In the present study, to determine whether salmon calcitonin would also show the same effects as elcatonin, and to get a suggestion about the role of calcitonin receptors in the anti-allodynic action of calcitonins, we tested the effect of salmon calcitonin on cold and mechanical allodynia induced by ad...

show abstract

“…10,11) Calcitonin also has the ability to relieve pain associated with a variety of disorders, including osteoporosis. [12][13][14][15][16] These actions are mediated by increased cAMP and intracellular Ca 2+ levels evoked by the stimulation of calcitonin receptors coupled to G proteins. [17][18][19] Cutaneous flushing is one of the most common side effects of calcitonin and the effects of elcatonin, a synthetic analog of eel calcitonin, 20) might be closely associated with plasma levels of vasoactive intestinal peptide.…”

mentioning

confidence: 99%

Vasodilator Effects of Elcatonin, a Synthetic Eel Calcitonin, on Retinal Blood Vessels in Rats

Mori

Suzawa

Sakamoto

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The aim of this study was to examine the effects of elcatonin, a synthetic derivative of eel calcitonin, on rat retinal blood vessels, and to determine how diabetes affects the retinal vascular responses. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal blood vessels contained in the digital images. Both systemic blood pressure and heart rate were continuously recorded. Elcatonin increased the diameter of retinal blood vessels but decreased mean blood pressure in a dose-dependent manner, whereas it had no significant effect on heart rate. A diminished retinal vasodilator response and significant pressor response to elcatonin were observed in rats injected intravenously with N G -nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor. Intravitreal injection of indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ22536, an adenylyl cyclase inhibitor, markedly attenuated the vasodilator effects of elcatonin on retinal blood vessels. The retinal vasodilator responses to elcatonin were unaffected 2 weeks after the induction of diabetes by a combination of streptozotocin treatment and D-glucose feeding. These results suggest that elcatonin dilates rat retinal blood vessels via NO-and COX-dependent mechanisms and that the adenylyl cyclase-adenosine 3′,5′-cyclic monophosphate system plays a major role in the vasodilator mechanisms. The retinal vasodilatory effects of elcatonin seem to be preserved at early stages of diabetes.Key words adenylyl cyclase; cyclooxygenase; nitric oxide; prostaglandin; retinal blood vessel Diabetic retinopathy is a leading cause of blindness in industrialized countries and is the most common complication of diabetes. Tight control of blood glucose levels decreases the risk of diabetic retinopathy onset and progression; however, additional effective treatments are still needed. The narrowing of retinal blood vessels and reduction in retinal blood flow are associated with the onset of diabetic retinopathy, and the impairment of retinal circulation contributes to the pathogenesis of the disease.1-4) Therefore, one strategy for preventing the disease or reducing its severity is to improve the impaired retinal circulation.Our previous studies demonstrated that adenosine 3′,5′-cyclic monophosphate (cAMP)-elevating agents dilate retinal blood vessels more effectively than peripheral resistance vessels.5,6) For example, prostaglandin (PG) I 2 and forskolin (an activator of adenylyl cyclase), which elevate intracellular cAMP levels, dilate retinal arterioles at doses much lower than that required to decrease systemic blood pressure. 5) A cAMP analog decreased systemic blood pressure less than that by an analog of guanosine 3′,5′-cyclic monophosphate (cGMP), though they produced a comparable vasodilation of retinal blood vessels. 6) These results suggested that cAMPelevating agents could be effective drugs for improving retinal circulation.Ca...

show abstract

Anti-Hyperalgesic Effects of Calcitonin on Neuropathic Pain Interacting with its Peripheral Receptors

Cited by 37 publications

References 35 publications

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats

Salmon Calcitonin Reduces Oxaliplatin-Induced Cold and Mechanical Allodynia in Rats

Vasodilator Effects of Elcatonin, a Synthetic Eel Calcitonin, on Retinal Blood Vessels in Rats

Contact Info

Product

Resources

About