Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Review Article

Calcitonin as an analgesic agent: review of mechanisms of action and clinical applications

Calcitonina como agente analgésico: revisão dos mecanismos de ação e das aplicações clínicas

Javad Yazdani, Reza Khorshidi Khiavi, Mohammad Ali Ghavimi, Ali Mortazavi, Elahe Jabbari Hagh, Farzin Ahmadpour

Downloads: 3
Views: 1195


Background and objectives
Calcitonin is a polypeptide hormone regulating the metabolism of calcium in the body. For many years calcitonin has been used to maintain and improve bone mineral density and to reduce the fracture rate. Many studies showed that calcitonin had analgesic role in several painful circumstances. This pain-ameliorating effect is irrelevant to its osteoclastic inhibitory effect and mechanisms like altering Na+ channel and serotonin receptor expression or hypothesis including the endorphin-mediated mechanism were used to explain this effect. In this study we performed a thorough review on the role of calcitonin as an analgesic agent in different scenarios and investigated the fact that calcitonin can be a feasible medication to relieve pain.

Many studies focused on the analgesic effect of calcitonin in several painful circumstances, including acute pains related to vertebral fractures, metastasis, migraine and reflex sympathetic dystrophy as well as neuropathic pains related to spinal injuries or diabetes, and phantom pain. Also, calcitonin was showed to be a useful additive to local anesthesia in the case of controlling postoperative pain or trigeminal neuralgia more effectively. However we faced some contradictory data for conditions like lumbar canal stenosis, complex regional pain syndrome, phantom pain and malignancies.

This study showed that calcitonin could be helpful analgesic agent in different painful situations. Calcitonin can be considered an eligible treatment for acute pains related to vertebral fractures and a feasible alternative for the treatment of the acute and chronic neuropathic pains where other medications might fail.


Calcitonin;  Acute pain;  Chronic pain;  Spinal fractures;  Malignancy;  Migraine;  Phantom pain;  Diabetic neuropathies


Justificativa e objetivos
A calcitonina é um hormônio polipeptídico que regula o metabolismo do cálcio no organismo. Por muitos anos a calcitonina tem sido usada para manter e melhorar a densidade mineral óssea e reduzir a incidência de fraturas. Muitos estudos mostraram que a calcitonina teve efeito analgésico em várias condições físicas de dor. Esse efeito de melhoria da dor é irrelevante diante de seu efeito inibidor osteoclástico e de mecanismos, tais como a alteração do canal de Na+ e da expressão do receptor de serotonina, incluindo a hipótese do mecanismo mediado pela endorfina, que foram usados para explicar esse efeito. Neste estudo, fizemos uma revisão completa sobre o papel da calcitonina como agente analgésico em diferentes cenários e investigamos o fato de que a calcitonina pode ser uma medicação viável para aliviar a dor.

Muitos estudos centraram no efeito analgésico da calcitonina em várias condições de dor, incluindo dores agudas relacionadas a fraturas vertebrais, metástases, enxaqueca e distrofia simpática reflexa, bem como dores neuropáticas relacionadas a lesões medulares ou ao diabetes e dor fantasma. Além disso, a calcitonina mostrou ser um aditivo útil à anestesia local para o controle mais efecaz da dor pós-operatória ou neuralgia do trigêmeo. Porém, nos deparamos com alguns dados contraditórios em condições como estenose do canal lombar, síndrome complexa da dor regional, dor fantasma e malignidades.

Este estudo mostrou que a calcitonina pode ser um analgésico útil em diferentes condições de dor. A calcitonina pode ser considerada um tratamento elegível para as dores agudas relacionadas a fraturas vertebrais e uma opção viável para o tratamento das dores neuropáticas agudas e crônicas em que outros medicamentos podem falhar.


Calcitonina;  Dor aguda;  Dor crônica;  Fraturas vertebrais;  Malignidade;  Enxaqueca;  Dor fantasma;  Neuropatias diabéticas


1 E. Kilinc, Y. Dagistan, A. Kukner, et al. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats Clin Exp Pharmacol Physiol, 45 (2018), pp. 536-546

2 J. Zhou, T. Li, L. Li, et al. Clinical efficacy of calcitonin compared to diclofenac sodium in chronic nonspecific low back pain with type I Modic changes: a retrospective study J Pain Res, 11 (2018), pp. 1335-1342

3 G.C. Wall, C.A. Heyneman Calcitonin in phantom limb pain Ann Pharmacother, 33 (1999), pp. 499-501

4 N.M. Mehta, A. Malootian, J.P. Gilligan Calcitonin for osteoporosis and bone pain Curr Pharm Des, 9 (2003), pp. 2659-2676

5 R.S. Perez, G. Kwakkel, W.W. Zuurmond, et al. Treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomized clinical trials J Pain Symptom Manage, 21 (2001), pp. 511-526

6 P.C. Braga Calcitonin and its antinociceptive activity: animal and human investigations 1975-1992 Agents Actions, 41 (1994), pp. 121-131

7 M. Azria Possible mechanisms of the analgesic action of calcitonin Bone, 30 (5 Suppl) (2002), pp. 80S-803S

8 A. Ito, M. Yoshimura Mechanisms of the analgesic effect of calcitonin on chronic pain by alteration of receptor or channel expression Mol Pain, 13 (2017), Article 174480691772031

9 T. Appelboom Calcitonin in reflex sympathetic dystrophy syndrome and other painful conditions Bone, 30 (5 Suppl) (2002), pp. 84S-86S

10 Z. Gabopoulou, A. Vadalouca, K. Velmachou, et al. Epidural calcitonin: does it provide better postoperative analgesia? An analysis of the haemodynamic, endocrine, and nociceptive responses of salmon calcitonin and opioids in epidural anesthesia for hip arthroplasty surgery Pain Pract, 2 (2002), pp. 326-331

11 N.A. Elsheikh, Y.M. Amr Calcitonin as an additive to local anesthetic and steroid injection using a modified coronoid approach in trigeminal neuralgia Pain Physician, 19 (2016), pp. 457-464

12 T.M. Fighera, P.M. Spritzer Effect of intranasal calcitonin in a patient with mccune- albright syndrome, fibrous dysplasia, and refractory bone pain Case Rep Endocrinol, 2017 (2017), Article 7898713

13 A. Ito, M. Yoshimura Mechanisms of the analgesic effect of calcitonin on chronic pain by alteration of receptor or channel expression Mol Pain, 13 (2017), Article 1744806917720316

14 Y. Terashima, T. Takebayashi, S. Jimbo, et al. Analgesic effects of calcitonin on radicular pain in male rats J Pain Res, 12 (2019), pp. 223-230

15 C.B. Yeh, S.J. Weng, K.W. Chang, et al. Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity Osteoporos Int, 27 (2016), pp. 3355-3364

16 G. Micieli, A. Cavallini, E. Martignoni, et al. Effectiveness of salmon calcitonin nasal spray preparation in migraine treatment Headache, 28 (1988), pp. 196-200

17 J.A. Knopp-Sihota, C.V. Newburn-Cook, J. Homik, et al. Calcitonin for treating acute and chronic pain of recent and remote osteoporotic vertebral compression fractures: a systematic review and meta-analysis Osteoporos Int, 23 (2012), pp. 17-38

18 L.A. Blau, J.D. Hoehns Analgesic efficacy of calcitonin for vertebral fracture pain Ann Pharmacother, 37 (2003), pp. 564-570

19 A. Ashraf, M. Khodadadi, A. Sadraei, et al. The efficacy of intramuscular calcitonin injection in the management of lumbar spinal stenosis Asian Spine J, 9 (2015), pp. 75-82

20 K. Haddadi, L. Asadian, A. Isazade 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, 9 (2016), pp. 133-138

21 V.K. Podichetty, A.M. Segal, M. Lieber, et al. Effectiveness of salmon calcitonin nasal spray in the treatment of lumbar canal stenosis: a double-blind, randomized, placebo-controlled, parallel group trial Spine (Phila Pa, 2004 (29) (1976), pp. 2343-2349

22 S.I. Tafazal, L. Ng, P. Sell Randomised placebo-controlled trial on the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis Eur Spine J, 16 (2007), pp. 207-212

23 A. Karponis, S. Rizou, D. Pallis, et al. Analgesic effect of nasal salmon calcitonin during the early post-fracture period of the distal radius fracture J Musculoskelet Neuronal Interact, 15 (2015), pp. 186-189

24 A. Rouhani, M. Mardani-Kivi, M. Bazavar, et al. Calcitonin effects on shoulder adhesive capsulitis Eur J Orthop Surg Traumatol, 26 (2016), pp. 575-580

25 M. Waldburger, J.L. Meier, C. Gobelet The frozen shoulder: diagnosis and treatment. Prospective study of 50 cases of adhesive capsulitis Clin Rheumatol, 11 (1992), pp. 364-368

26 S. Brue, A. Valentin, M. Forssblad, et al. Idiopathic adhesive capsulitis of the shoulder: a review Knee Surg Sports Traumatol Arthrosc, 15 (2007), pp. 1048-1054

27 J. Szanto, S. Jozsef, J. Rado, et al. Pain killing with calcitonin in patients with malignant tumours Oncology, 43 (1986), pp. 69-72

28 M.J. Martinez-Zapata, M. Roque, P. Alonso-Coello, et al. Calcitonin for metastatic bone pain Cochrane Database Syst Rev, 3 (2006), Article CD003223

29 M. Schurmann, T. Vogel, A. Gartner, et al. Experiences with calcitonin treatment of patients with type I complex regional pain syndrome (CRPS I ‒ Sudeck disease) Z Orthop Ihre Grenzgeb, 139 (2001), pp. 452-457

30 F. Sahin, F. Yilmaz, N. Kotevoglu, et al. Efficacy of salmon calcitonin in complex regional pain syndrome (type 1) in addition to physical therapy Clin Rheumatol, 25 (2006), pp. 143-148

31 S. Matayoshi, M. Shimodozono, Y. Hirata, et al. Use of calcitonin to prevent complex regional pain syndrome type I in severe hemiplegic patients after stroke Disabil Rehabil, 31 (2009), pp. 1773-1779

32 C. Gobelet, M. Waldburger, J.L. Meier The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy Pain, 48 (1992), pp. 171-175

33 W.S. Kingery A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes Pain, 73 (1997), pp. 123-139

34 R. Viana, M.W. Payne Use of calcitonin in recalcitrant phantom limb pain complicated by heterotopic ossification Pain Res Manag, 20 (2015), pp. 229-233

35 T. Turek, A. Wigton Calcitonin for phantom limb pain in a pregnant woman Am J Health Syst Pharm, 69 (2012), pp. 2149-2152

36 I. Bharwani, A. Rajagopal, J. Ray Use of calcitonin to treat phantom limb pain Hosp Phys (2003), pp. 46-50

37 H. Jaeger, C. Maier Calcitonin in phantom limb pain: a double-blind study Pain, 48 (1992), pp. 21-27

38 U. Eichenberger, F. Neff, G. Sveticic, et al. Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds Anesth Analg, 106 (2008), pp. 1265-1273 table of contents

39 A. Trombetti, F. Cortes, A. Kaelin, et al. Intranasal calcitonin reducing bone pain in a patient with Camurati-Engelmann disease Scand J Rheumatol, 41 (2012), pp. 75-77

40 S.R. Humble Calcitonin for acute neuropathic pain associated with spinal cord injury Anaesth Intensive Care, 39 (2011), pp. 682-686

41 G. Schwartz, M. Galonski, A. Gordon, et al. Effects of salmon calcitonin on patients with atypical (idiopathic) facial pain: a randomized controlled trial J Orofac Pain, 10 (1996), pp. 306-315

42 W. Zieleniewski Calcitonin nasal spray for painful diabetic neuropathy Lancet, 336 (1990), p. 449

43 A. Quatraro, A. Minei, N. De Rosa, et al. Calcitonin in painful diabetic neuropathy Lancet, 339 (1992), pp. 746-747

44 E.J. Visser, P.L. Kwei Salmon calcitonin in the treatment of post herpetic neuralgia Anaesth Intensive Care, 34 (2006), pp. 668-671

45 G. Papadokostakis, J. Damilakis, E. Mantzouranis, et al. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis Eur Spine J, 15 (2006), pp. 356-362

46 D. Ofluoglu, G. Akyuz, O. Unay, et al. The effect of calcitonin on β-endorphin levels in postmenopausal osteoporotic patients with back pain Clin Rheumatol, 26 (2006), pp. 44-49

47 L. Lucchesi, J. Kwok Long term antibiotics and calcitonin in the treatment of chronic osteomyelitis of the mandible: case report Br J Oral Maxillofac Surg, 46 (2008), pp. 400-402

48 J. Yazdani, F. Ahmadpour Effect of calcitonin on the pain relief in patients with maxillofacial fractures [Defended Doctorial Thesis] Dentistry faculty: Tabriz Medical University (2019)

49 Z.L. Qin, L.Q. Yang, N. Li, et al. Clinical study of cerebrospinal fluid neuropeptides in patients with primary trigeminal neuralgia Clin Neurol Neurosurg, 143 (2016), pp. 111-115

50 Y.J. Yang, L. Hu, Y.P. Xia, et al. Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK J Neuroinflamm, 13 (2016), p. 84

51 M. Ustdal, P. Dogan, A. Soyuer, et al. Treatment of migraine with salmon calcitonin: effects on plasma beta-endorphin, ACTH and cortisol levels Biomed Pharmacother, 43 (1989), pp. 687-691

52 C.H. Chesnut 3rd, M. Azria, S. Silverman, et al. Salmon calcitonin: a review of current and future therapeutic indications Osteoporos Int, 19 (2008), pp. 479-491

53 S.M. Zolhavarieh, S.H. Mousavi-Bahar, M. Mohseni, et al. Effect of intravenous acetaminophen versus fentanyl on postoperative pain after transurethral lithotripsy Rev Bras Anestesiol, 69 (2019), pp. 131-136

54 F. Coluzzi, R. Taylor Jr., J.V. Pergolizzi Jr., et al. Good clinical practice guide for opioids in pain management: the three Ts ‒ titration (trial), tweaking (tailoring), transition (tapering) Braz J Anesthesiol, 66 (2016), pp. 310-317

55 P. Wiffen, S. Collins, H. McQuay, et al. Anticonvulsant drugs for acute and chronic pain Cochrane Database Syst Rev (3) (2005), Article CD001133

56 A.C. Hindley, E.B. Hill, M.J. Leyland, et al. A double-blind controlled trial of salmon calcitonin in pain due to malignancy Cancer Chemother Pharmacol, 9 (1982), pp. 71-74

57 A. Roth, K. Kolaric Analgetic activity of calcitonin in patients with painful osteolytic metastases of breast cancer. Results of a controlled randomized study Oncology, 43 (1986), pp. 283-287

58 C. Gennari, L. Bocchi, C.A. Orso, et al. The analgesic effect of calcitonin in active Paget’s disease of bone and in metastatic bone disease Orthopedics, 7 (1984), pp. 1449-1452

59 C. Gennari Analgesic activity of salmon and human calcitonin against cancer pain: a double-blind, placebo controlled clinical study Cur Ther Res, 38 (1985), pp. 298-303

60 C. Gennari Calcitonin in bone pain management Curr Ther Res, 44 (1988), pp. 712-722

61 G.F. Schiraldi, E. Soresi, S. Locicero, et al. Salmon calcitonin in cancer pain: comparison between two different treatment schedules Int J Clin Pharmacol Ther Toxicol, 25 (1987), pp. 229-232

62 P. Liu, D.Q. Yang, F. Xie, et al. Effect of calcitonin on anastrozole-induced bone pain during aromatase inhibitor therapy for breast cancer Genet Mol Res, 13 (2014), pp. 5285-5291

63 F. Fraioli, A. Fabri, L. Gnessi, et al. Subarachnoid calcitonin for intolerable pain Lancet, 2 (1982), p. 831

64 N. Tsavaris, P. Kopterides, C. Kosmas, et al. Analgesic activity of high-dose intravenous calcitonin in cancer patients with bone metastases Oncol Rep, 16 (2006), pp. 871-875

65 C. Blomqvist, I. Elomaa, L. Porkka, et al. Evaluation of salmon calcitonin treatment in bone metastases from breast cancer ‒ a controlled trial Bone, 9 (1988), pp. 45-51

5e45a0710e8825926f59a71f rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections