Capsaicin

Mechanism of Action

Capsaicin, a member of the vanilloid family, is a group of compounds that possess a vanillyl group. It binds as an agonist to vanilloid receptor subtype 1 (TRPV1 - transient receptor potential V1), which is an ion channel type trans-membrane receptor. The TRPV1 receptor also is stimulated by temperature changes, physical abrasion, pH changes, and endogenous lipids. When activated, it starts a depolarization cascade that allows the influx of sodium and calcium ions. TRPV1 receptors are found on C- and A-delta fibers in the nociceptive sensory pathway. When depolarization occurs along fibers, signals propagate into the spinal cord to the brain. 

Capsaicin reduces pain transmission by desensitizing the sensory afferent axons. This phenomenon occurs due to the high permeability of the TRPV1 channels for calcium ions. This excess influx of calcium causes loss of mitochondrial function (as well as other cellular organelles) and thus renders the afferent nerve fiber inoperant.[9]

As these nerve fibers lose functionality, all of the mediators produced within these fibers will also show a marked decrease. One of these substances is a well-known potent local pain mediator, substance P. 

Constant usage of capsaicin further promotes calcium influx into more of these nociceptive nerve fibers. This promotes preformed substance P release during the first applications, which causes initial neurogenic inflammation, but after repeated application, capsaicin depletes the neuron of substance P, and the further inoperability of the cell prevents it from forming more of this pain chemo-mediator.

An alternative mechanism of analgesia is suggested by studies using a potent capsaicin analog, resiniferatoxin. Activation of TRPV1 receptors by resiniferatoxin (RTX) results in a sustained rise in free intracellular calcium levels, which leads to calcium-induced cytotoxicity and the selective death of cells bearing TRPV1 receptors. RTX produced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons in cultures of human dorsal root ganglion, but adjacent non-TRPV1 bearing neurons were not affected.[10] The authors of the study suggested that nociceptive neuronal or nerve terminal deletion may be an effective strategy for pain management.

Administration

Capsaicin is administered in many forms such as low-concentration creams, lotions, patches, intradermal injections, oral formulations, subcutaneous injections, intravenous, films, microemulsions, liposomes, and nanotechnology-derived drug delivery systems.

Adverse Effects

The more common potential adverse reactions and events with topical patch administration include local erythema, local pain, local pruritus, local edema, local swelling, local dryness, hypertension, papules, pruritus, nausea, vomiting, nasopharyngitis, sinusitis, bronchitis.

The more rare complications include abnormal skin odor, cough, dizziness, dysgeusia, headaches, hypesthesia, peripheral edema, peripheral sensory neuropathy, and throat irritation.

Contraindications

Some studies have reported relative contraindications in patients with asthma, as they have greater sensitivity to capsaicin. It is presumed that there is increased TRPV1 activity in asthmatics with an increase in endovanilloids in the airways. There are, however, no reported absolute contraindications to the use of capsaicin.

Monitoring

The therapeutic index for topical and oral capsaicin has not been well studied; however, it is known that exposure to high doses, above 100 mg per kg body weight, of capsaicin for a prolonged time can cause peptic ulcers, enhance breast cancer metastasis, and accelerate the development of prostate, stomach, duodenal, and liver cancer. Also, it is advised to not apply it immediately before or after activities such as bathing, swimming, sunbathing, or strenuous exercise and to avoid getting it on mucous membranes or eyes.

Toxicity

From a review of the literature, it appears the acute toxicity of capsaicin is determined only in animal species. A study in mice has shown that application of capsaicin based on LD50 values greater than 9 mg/kg (subcutaneous) or 190 mg/kg (by mouth), the likely mechanism of toxicity involves respiratory paralysis. There is no known reported case of an overdose in humans, and there is no known antidote.

Acute Toxicity

Capsaicin is a potent irritant, and if exposed to the mucous membranes, it can cause severe irritation, pain, and burning. When it gets in the eye, capsaicin can cause prolonged burning pain with tearing, photophobia, and blurry vision. When inhaled, it can cause dry coughing spells, wheezing, and dyspnea.

Most people who present to the emergency department after acute exposure to capsaicin complain of burning pain on the skin. Children have reported side effects of nausea, vomiting, diarrhea, and abdominal cramps.

Some people who have used capsaicin to lose weight have presented to the emergency department with profuse diaphoresis and chest pain. In these patients, reports of myocardial ischemia have been reported. 

If acute exposure has occurred, first remove the patient from further exposure. All contaminated clothing should be removed and placed in an airtight container. If the eyes or nose have been exposed, one should bathe the mucous membrane with oils like petroleum jelly or vegetable oil. To relieve the abdominal symptoms, polyethylene glycol or cold milk has been recommended. Skin exposure can be limited by washing the area with detergent followed by a thorough rinse with water. Just plain water alone is not effective at removing capsaicin from the skin.

If the patient has wheezing, one may need to use intravenous corticosteroids and nebulizer therapy.

It is highly recommended that healthcare workers wear gloves and goggles when handling and applying topical capsaicin on the skin of patients.

Enhancing Healthcare Team Outcomes

Managing drug side effects requires an interprofessional team of healthcare professionals, including clinicians, mid-level practitioners, nurses, and pharmacists. Without proper instruction on use, capsaicin can cause burning or stinging pain to the skin and, if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, conjunctivitis, and blepharospasm. Proper use of capsaicin under interprofessional guidance can be beneficial to patient outcomes. [Level 5]