Does Calcitonin Help Relieve Neuropathic Pain?

Jeffrey Fudin, BS, PharmD


January 29, 2009

Is there evidence that supports the use of salmon calcitonin in treating neuropathic pain?

Response from Jeffrey Fudin, BS, PharmD
Adjunct Associate Professor, Albany College of Pharmacy/Union University, Albany, New York; Clinical Pharmacy Specialist, Stratten VA Medical Center, Albany, New York

Calcitonin-salmon (Miacalcin®) is indicated for hypercalcemia, Paget's disease, and postmenopausal osteoporosis.[1] Unlabeled use of calcitonin has been examined for osteoporosis-related vertebral fracture pain,[2]metastatic bone pain,[3]trigeminal neuralgia,[4] and phantom limb pain (PLP).[5] Generally, nonmammalian calcitonin used intranasally appears to be more effective than mammalian calcitonin or calcitonin used by the injectable route.[6]

Several mechanisms have been suggested for the antinociceptive effect of calcitonin. The drug may be centrally acting by exerting actions on serotonin[7]; calcitonin receptor mRNA has been elucidated on serotonergic neurons associated with pain processing.[8] Although calcitonin does not seem to alter the synthesis and metabolism of serotonin, it does require the serotonin system for its analgesic effects.[9] Increases in serum beta-endorphin levels caused by calcitonin may also contribute to analgesia, presumably because of an association with opiate receptor uptake.[6] Proposed mechanisms for the peripheral action of calcitonin include reduced local production of inflammatory prostaglandins and cytokines involved in pain generation.[7]

To recognize the role of any analgesic in neuropathic pain, one must first understand that neuropathic pain is very complex, may involve tissue injury, and is generally the result of nervous system dysfunction.[10] Depending on the specific location(s) of damage (ie, axonal, receptor, neuro-amine dysfunction, synapse) and whether the process involves peripheral and/or central nerve fibers, the symptomatic result may involve the site of injury and/or surrounding tissues.

Neuropathic pain is stimulus-independent and characterized by allodynia and paresthesias.[10]Two very different examples of neuropathic pain include PLP and fibromyalgia. PLP is thought to occur because of a "hard wiring" within the central nervous system and is also affected by erroneous nerve growth following an amputation. Fibromyalgia has recently been considered a neuropathic pain syndrome because of sympathetic stimulation.[10,11]

In 1 case, a 79-year-old male patient with a history of PLP subsequent to a right, above-knee amputation experienced a severe exacerbation of the pain after spinal anesthesia for percutaneous laser angioplasty of the left superficial femoral artery. The PLP intensity remained excruciating postoperatively. Five minutes after the administration of intravenous salmon calcitonin 100 international units (IU), the pain had entirely abated. The PLP had returned to baseline at follow-up several months later.[12]

An open-label trial evaluating salmon calcitonin for PLP was conducted involving 10 patients who had undergone amputation and had either constant or paroxysmal PLP. These patients were given a single intravenous injection of salmon calcitonin 100 IU over 5 minutes. None of these patients were given any other analgesic in the 6 hours prior to calcitonin administration. Nine of the 10 patients reported immediate and significant pain relief within 30 minutes of receiving the injection. The most common reported side effects included nausea and vomiting.[13]

A double-blind, placebo-controlled study with a crossover design was conducted in 21 patients in whom PLP developed after surgical amputation. Patients received either salmon calcitonin 200 IU infused over 20 minutes or placebo. Each group served as its own control; the active drug and placebo injections were administered in a blinded fashion in random sequence. After the patients received the calcitonin, 90% reported pain relief of at least 50%. Seventy-six percent of all patients reported that subsequent to the injection, they were pain-free. Nausea and vomiting were reported in 6 patients and were considered to be mild and transient.[14]

A phase IV study being conducted by Ramos-Remus and colleagues[15] is currently investigating the use of intranasal salmon calcitonin for the treatment of fibromyalgia. This study began in October 2008 and is expected to conclude in June 2009.

In conclusion, limited evidence suggests that salmon calcitonin may be effective in producing analgesia in certain conditions. However, more studies are needed to evaluate the safety and efficacy of calcitonin in treating neuropathic pain.

The author wishes to acknowledge Elena G. Napper, student pharmacist, Albany College of Pharmacy, Albany, New York.


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