Counterirritant

Conventional and novel PKC isozymes are potently activated by phorbol esters, heterocyclic compounds found in the milky sap exuded by plants of the Euphorbiaccae family. This sap was used medicinally as a counterirritant and cathartic agent over the millennia we now know that the active ingredients, phorbol esters, specifically bind to the Cl domain, the diacylglycerol sensor described above. In fact, their ability to recruit PKC to membranes is so effective that phorbol esters cause maximal activation of conventional PKCs, bypassing the requirement for Ca2+. This module is found in a number of other proteins in addition to PKC, so the profound effects of phorbol esters on cells are mediated by other proteins in addition to PKC. 

Topical analgesics sometimes are used for mild pain or as an adjunct to systemic therapy. There are limited data to support the use of salicylate-containing rubefacients (e.g., methyl salicylate and trolamine salicylate) or other counterirritants (e.g., menthol, camphor, and methyl nicotinate) in OA.32 See Chap. 57 for more information on these products when used for musculoskeletal disorders. 

Identify the factors that guide selection of an analgesic or counterirritant for a particular patient. 

Patient education on proper use of counterirritants is essential to therapeutic success. 

Theoretically, the risk of serious GI adverse events should be less than with oral NSAIDs, but long-term studies evaluating these events are lacking.38 Studies comparing topical NSAIDs with other topical products, including counterirritants, are also needed.35 Local cutaneous adverse reactions (e.g., erythema, pruritus, and irritation) occur in 1% to 2% of patients and may be due in part to the vehicle used.38... 

Counterirritants are categorized by the Food and Drug Administration (FDA) into four groups (groups A-D) based on their primary actions (Table 57-2). They produce a feeling of warmth, cooling, or irritation that diverts sensation from the primary source of pain. Because these irritant effects are central to the beneficial actions, counterirritants should not be combined with topical anesthetics or topical analgesics. 

Counterirritants are approved for the temporary relief of minor aches and pains related to muscles and joints.24 These symptoms may be associated with simple backache, arthritis, strains, sprains, or bruises. Many are available commercially as combination products with ingredients from different counterirritant groups. Active ingredients in marketed products sometimes change clinicians should be aware of the current ingredients before providing a product recommendation. 

Application of topical salicylates can lead to systemic effects, especially if the product is applied liberally. Repeated application and occlusion with a wrap or bandage also can increase systemic concentrations.41 Salicylate-containing counterirritants should be used with caution in patients in whom systemic salicylates are contraindicated, such as patients with severe asthma or aspirin allergy.42 Topical salicylates have been reported to increase prothrombin time in patients on warfarin and should be used with caution in patients on oral anticoagulants.43... 

The group C counterirritants methyl nicotinate and histamine dihydrochloride produce vasodilation.24 Methyl nicotinate is a nicotinic acid derivative that produces prostaglandin-mediated vasodilation.46 NSAIDs and aspirin block the production of prostaglandins and decrease methyl nicotinate-induced vasodilation. Application over a large area has been reported to cause systemic symptoms and syncope, possibly due to vasodilation and a decrease in blood pressure.47 Patients should be educated to apply only scant amounts to the affected area to avoid this effect. 

The primary counterirritant in group D is capsaicin, a natural substance found in red chili peppers and responsible for the hot, spicy characteristic when used in foods.32,33,48 Capsaicin stimulates the release of substance P from local sensory nerve fibers, depleting substance P stores over time. A period of reduced sensitivity to painful stimuli follows, and transmission of pain impulses to the central nervous system is reduced.42... 

As with other counterirritants, capsaicin and its derivatives (i.e., capsicum and capsicum oleoresin) exert a warming or burning sensation. With repeated application, desensitization occurs, and the burning sensation subsides. This typically occurs within the first 1 to 2 weeks. After discontinuation,... 

Recommend appropriate pharmacologic therapy and educate on proper use. If a counterirritant is recommended, counsel patients on the irritant effect of the product and recommend washing hands immediately after use and to avoid heating pads. For patients using a capsaicin product, emphasize that adherence to regular application is required for effectiveness. 

Rubefacient An agent applied to the skin that causes local irritation and redness used to relieve pain by a counterirritant mechanism. 

Ukraine. Hot water extract of dried plant is taken orally for bronchial asthma . United States. Infusion of the fruit-fixed oil is taken orally to treat hypertension and agitation. Extract of the fruit-fixed oil is taken orally as a mild laxative and vermicide and taken externally as a counterirritant L Yugoslavia. Hot water extract of the dried leaf is taken orally for diabetes . 

Turpentine oil, from species of pines, used as a counterirritant. 

N.A. Daphne mezereum L. D. genkwa Sieb. et Zucc. Diterpenes (daphnetoxin, mezerein), mucilage, tannins." This herb is toxic. As an external counterirritant only, for rheumatic joints. 

Arnica is believed to have topical counterirritant properties. It is used for unbroken chilblains (swelling of the hands and feet from exposure to damp cold), alopecia neurotica, and specifically for sprains and bruises. It is mainly used in homeopathic preparations and, to a lesser extent, in herbal products. 

Capsicum has stimulant, antispasmodic, carminative, diaphoretic, counterirritant, antiseptic, and rubefacient properties. Traditionally, it has been used for colic, flatulent dyspepsia without inflammation, chronic laryngitis (as a gargle), insufficiency of peripheral circulation, and externally for neuralgia, including rheumatic pains and unbroken chilblains. 

Clove has been traditionally used as a carminative, antiemetic, toothache remedy, and counterirritant. Clove oil is believed to be a carminative, occasionally used in the treatment of flatulent colic, and is commonly used topically for symptomatic relief of toothache. 

Black mustard is a light olive-brown powder obtained by grinding the dried ripe seeds of several varieties of plants of the Brassica genus moisture yields from this, through enzymatic hydrolysis of a contained glycoside, are about 0.6% of the volatile oil of mustard, which has as its main ingredient the irritant compound allyl isothiocyanate. Mustard is available in bulk and as the official plaster, the latter used only for the local irritant (counterirritant) properties it develops when applied to the skin after moistening with tepid water. 

Used as a counterirritant in sore muscles, bruises, sprains, and strains... 

Capsaicin (cap-say -i-sin). Also called capsicum, capsaicin is the main ingredient found in many hot peppers (Figure 6.2) and spices such as paprika and cayenne pepper. Capsaicin is also the active ingredient in self-defense products such as pepper spray. Capsaicin directly activates nociceptors located on nerve fibers, and thus it would seem to be counterproductive (if not crazy) to apply such a substance on a wound to relieve pain. However, it turns out that capsaicin creams, gels, and lotions are indeed effective pain relievers and counterirritants when applied topically to the skin. 

Safrole is found in oils of camphor and saffras. It has been used medicinally as a counterirritant and for parasitic infections. It is also a listed carcinogen and cannot be used as a fragrance ingredient. 

Argent Nitras (nitrate of silver) Sometimes referred to as lunar caustic, it was given topically and internally. Used externally as a counterirritant used internally for dyspepsia, diarrhea, croup, cough, tonsillitis, and other affections of the throat, ophthalmic conditions, and even reportedly used for gonorrhea. 

Cantharides (Spanish fly) This beetle, when pulverized, produced a poultice that caused blistering and was considered a counterirritant. Used topically for cutaneous eruptions, obstinate herpes, erysipelas, and other local inflammations. 

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