Ointment with capsaicin: effective help for joints (instructions, price and reviews)

What is capsaicin?

The ointment contains a capsicum alkaloid with the same name, capsaicin. This is a substance that is insoluble in water. It is quite hot. That is why the drug based on it has a warming effect when applied. A reaction with certain chemical components or an alcoholic medium can dissolve this alkaloid.

Chemical formula of capsicin

Applying a product based on it to open skin can cause a burn. In this case, the drug can be washed off only with oils, acetic acid or alcohol-containing liquids. A similar hood is used to refill gas cartridges used in self-defense.

When it comes into contact with the mucous membrane of the mouth or eyes, the effect of capsaicin causes a severe burning sensation, which deprives a person of the ability to act purposefully.

The pepper substance has also found use in medicine. It is also used to prepare chemical mixtures that kill pests and some types of pathogenic microorganisms.

Capsaicin

Capsaicin is the active component obtained from the fruit of capsicum or cayenne pepper. It has been used in traditional medical systems to relieve muscle and arthritic pain, as well as to treat cluster headaches and psoriasis. For these purposes, capsaicin is the active ingredient in some topical creams and nasal sprays. It is also available as a prescription patch. Oral formulations are sold primarily to treat digestive and circulatory problems, poor appetite, and weight loss. (See cayenne pepper)

Research supports the benefits of low-concentration topical capsaicin for psoriasis (1), pruritus nodosum (2), and pruritus anal (3). It is also conditionally recommended for osteoarthritis (4), and a meta-analysis suggests that it may be as effective as topical NSAIDs for osteoarthritis (44), but its usefulness in rheumatoid arthritis remains inconclusive (5). An earlier clinical study shows that 0.075% capsaicin cream can control postoperative pain in cancer patients (6). A case report of a palliative care patient using capsaicin 0.025% for the treatment of opioid-refractory upper extremity pain also reported benefit (7).

A patch with a high concentration of dermal capsaicin has been shown to be safe and effective for postherpetic neuralgia (8) and has been approved for prescription use. Data also suggest that it is superior to pregabalin (45) and is effective for diabetic peripheral neuropathy (36), heterogeneous neuropathic pain (37), and neuropathic pain resulting from radiculopathy (38), but not for HIV-associated neuropathic pain (9 ). A recent systematic review suggests some benefits in both postherpetic neuralgia and HIV neuropathy compared with controls. However, the patch is best used when other treatments have failed due to the small number of patients likely to benefit (1 in 8) and unknown risks (10). It has been determined that low concentrations of capsaicin are unlikely to have meaningful use for these conditions in clinical practice (11). Data are also limited in patients with neuropathy after mastectomy (12).

A preliminary study suggests improved swallowing function in elderly patients with dysphagia when 0.025% capsaicin ointment was applied to the external auditory canal (43). Other reports, several case series suggest that topical capsaicin may be effective in cannabis-associated hyperemesis (39) (42). Only a few small studies suggest that intranasal capsaicin in various forms may be useful for rhinitis (13) (14), and its effectiveness for cluster headaches is unknown (15).

There is ongoing debate as to whether capsaicin acts as a carcinogen, co-carcinogen, or anti-carcinogen (16)(17)(18). For example, capsaicin has demonstrated chemopreventive and antiproliferative effects against various cell lines, including breast (19), bladder (20), and prostate (21) cancer cells. Additionally, a small study suggests the utility of a high-concentration dermal capsaicin patch for relieving pain associated with chemotherapy-induced peripheral neuropathy (CIPN) (40). However, long-term topical application has been shown to increase skin carcinogenesis in tumor promoter-treated mice (18), although such effects may be concentration dependent (22). Therefore, more research is needed to clarify the role of capsaicin in cancer.

Drugs containing capsaicin and their effects

Hot pepper extract is present in some medicinal preparations. They can have different release forms, but are in direct contact with the skin, which has a warming effect. Preparations with capsaicin can be found in the form of:

• Mazey
• Gels
• Plasters
• Rubbing

Pepper-based products are used exclusively externally. Their internal use can lead to injury to the mucous membranes or stomach upset.

External forms of release, such as cream or ointment, have a targeted effect directly on the site of inflammation, cause a minimal number of adverse reactions and relieve pain. All that remains is to choose the most suitable capsaicin-based remedy from the list of proposed medications.

In preparations of this kind, the pepper content is low - no more than 10%. But the effectiveness of the action provided is still at its best.

From ointments with capsaicin you can choose:

1. Nicoflex
2. Efkamon
3. Camphocin
4. Rescuer Forte
5. Espaul
6. Capsicam
7. Joint

Ointment with capsaicin "Nikoflex"
The names of the drugs are different, but the principle of action is similar. In each of them, the active substance in the composition is capsaicin. When choosing the most suitable drug, you should take into account possible contraindications and personal tolerance to the ingredients of the ointments.

Storage conditions and periods

Pharmacy creams or gels with the addition of capsicaicin are usually stored at a temperature not lower than room temperature. Permissible mode up to 30 degrees. Avoid direct sunlight on the drug tube. It should not be stored in close proximity to heating appliances.

Medicines should not be kept in the bathroom. Make sure that the place allocated for their storage is inaccessible to children and pets.

Indications for use

The instructions for medications containing pepper extract indicate indications for their use. The main effect of such drugs is pain relief and warming up.

Capsicin-based drugs are indicated for joint and back pain. They are used for:

1. Pain in the spine, lower back or back
2. Joint pain
3. Migraines
4. Osteoarthritis
5. Sciatica
6. Tendinitis
7. Herpes zoster

Capsaicin also helps in the fight against neuropathic pain. When applied to the surface of the skin, temporary relief of the symptoms of these disorders occurs. Ointments are prescribed for sprains, bruises and dislocations.

The effect of using such drugs is good, but short-lived. The effect is most rapid on lesions located in close proximity to the surface of the skin.

Contraindications and side effects of drugs containing capsaicin

Medicines based on capsaicins are sold in pharmacies without presenting a prescription. When purchasing, you should pay attention to existing contraindications.

If the skin is highly sensitive and there are open wounds, it is strictly forbidden to use products with capsicin. There are actually not that many of them:

• Age limit (not younger than 6 years old)
• Hypersensitivity to the components of the composition
• Impaired integrity of the skin
• Pregnancy and breastfeeding

Children under 18 years of age should use the ointment only after prior consultation with a doctor. When treating other concomitant diseases, interactions with other drugs should be considered. The use of drugs containing capsaicin may cause the following adverse reactions:

1. Burning feeling
2. Itching
3. Pain and redness at the application site
4. Headache
5. Increased pressure
6. The appearance of papules and blisters
7. Skin irritation
8. Allergic reaction

If it gets on the mucous membranes, the burning sensation will be very strong and can even cause a burn. When applying preparations containing hot pepper, you should be extremely careful. If the use of the cream causes reactions not described in the instructions, you should stop using the product and visit a doctor.

Overdose

Cases of overdose are practically excluded, because you regulate the volume of cream applied yourself. If the dosage is exceeded, adverse reactions develop. In this case, the cream should be washed off the skin.

Rules for the use of drugs with capsaicin

In addition to the recommendations contained in the instructions for use, you should follow simple rules that allow you to safely use the drug containing a burning component.

Before using the ointment, it is important to make sure that you are not allergic to capsaicin. If there are no contraindications, follow the following rules for using products containing capsaicin:

1. Before the first application, perform an allergy test.
2. The layer when rubbing the cream should be as thin as possible.
3. The combined use of warming cream and dressings with a similar principle of action should be avoided.
4. After applying the cream, hands should be washed with soap.
5. The ointment is removed from the skin using vinegar, alcohol or oil.
6. After application to the skin, the ointment should not be inhaled.

You should not apply cream, one of the components of which is hot pepper, to the skin after taking a bath or shower. You should avoid smearing areas of the skin with tissue damage, as well as in areas of inflammation .

special instructions

In diabetic neuropathy, ointments with capsaicin should be used with caution.
Capsaicin-based drugs do not affect the ability to perform high-risk work or control vehicles and machinery. The treatment course allows the consumption of alcoholic beverages. Caution should be exercised in patients with diabetic neuropathy.

Price

The price of capsaicin ointments may vary. Any of them is sold in pharmacies without a prescription. The cost depends on the volume of the product in the tube, the manufacturer and the markup of the pharmacy chain.

Here are the approximate prices of some ointments:

• Nicoflex – from 300 rub.
• Capsicam - from 310 rub.
• Joint – from 200 rub.

According to the results of numerous studies, antiepileptic drugs and antidepressants are the drugs of choice for the treatment of neuropathic pain (NP). Their widespread use is often limited due to side effects from the central nervous system, a long dose titration period, and the need to take into account drug interactions (Table 1)

.

This is especially true in elderly patients, who often have concomitant diseases and require polypharmacotherapy. In addition, many patients have to use combinations of painkillers, since according to the results of clinical studies, the effectiveness of each individual drug does not exceed 50% (with the exception of carbamazepine, the effectiveness of which for trigeminal neuralgia reaches 69%) [1-3]. Side effects such as drowsiness, dizziness, decreased concentration, as well as the need to re-take medications throughout the day reduce the quality of life of patients and can reduce their adherence to treatment. An alternative in cases of regional NB may be the use of local analgesics. For this purpose, transdermal forms of lidocaine and capsaicin are currently widely used, but the possibilities of their clinical use are limited due to the need for multiple applications. In addition, dosage forms of low-dose capsaicin cause local skin reactions, its vapors have an irritating effect on the mucous membranes, and the effectiveness is not always sufficient [4, 5]. At the same time, clinical studies of a new medicinal form of capsaicin containing the active substance in a high dose (8%) in the form of a patch have demonstrated some of the best results among existing drugs in the treatment of postherpetic neuralgia (PHN) and other forms of NP [6].

Peripheral mechanisms of NB

NB is a common pathological condition, observed in approximately 5% of individuals [7, 8]. BN occurs as a result of damage to the somatosensory nervous system in the peripheral or central nervous system [9]. NB is characterized by the simultaneous presence of both “loss” symptoms, i.e. reduction or loss of sensitivity, as well as “positive” phenomena, which include spontaneous pain in the absence of any stimuli, paresthesia and an altered response to a stimulus - allodynia (when a low-threshold non-painful stimulus provokes pain), and hyperalgesia (increased sensitivity to low-level painful stimuli). intensity) [10]. A combination of negative and positive phenomena is quite common in neurological diseases; for example, degeneration of the substantia nigra is accompanied by the development of tremor, and when the pyramidal tract is damaged, spasticity occurs [11]. However, compared with these movement disorders, pain is a subjective sensory phenomenon that is difficult to measure objectively, and the assessment of pain must take into account not only physical, but also psychological and emotional aspects. Typical complaints with NB are burning sensations, tingling, electric current, shooting pain, etc. Although these characteristics are not completely pathognomonic, their combination indicates a high probability of NB.

NP can occur due to various causes and pathological conditions, while the mechanisms of its development often do not depend directly on the cause of the disease: the same mechanism can be observed in various diseases (for example, with PHN and painful polyneuropathy) and, conversely, various pathological conditions can be accompanied by the occurrence of similar symptoms [11, 12].

Ligand-mediated and voltage-gated ion channels in the development of NB

The leading mechanism for the development of NB with damage to the peripheral nervous system is considered to be a change in the activity of ion channels of unmyelinated C-fibers and weakly myelinated Aδ-fibers, i.e. nociceptors [13]. The increased firing of these fibers overcomes the threshold of excitation of secondary neurons in the dorsal horn of the spinal cord, causing further propagation of pain signals in the central nervous system [10]. There are ion channels that are directly involved in the perception of a stimulus, changing the charge of the membrane and/or activating certain processes in the cell with the participation of secondary messengers, and fast sodium channels that generate action potentials [13]. An example of the former is the TRP family of ion channels, formed by six loops that span the cell membrane and form a channel that selectively conducts calcium and magnesium ions to a greater extent, but not sodium. The first type of channel, which is associated with the transmission of pain signals (TRPV1), is activated by exposure to high temperature, capsaicin and low pH [14, 15]. Several types of TRP channels have been shown to be expressed by sensory neurons. Each of them is tuned to perceive specific physical or chemical stimuli, in particular thermal influences in the temperature range from painless heat (TRPV3) to high temperatures that cause pain (TRPV2). Subpopulations of nociceptors express ion channels in complex patterns, and it is these differences in expression that determine the physiological heterogeneity of nociceptors. For example, some nociceptors respond to painful, thermal, mechanical and chemical stimuli (multimodal nociceptors), while others are insensitive to mechanical and thermal stimuli until their response threshold is altered by inflammatory mediators [16].

Subsequently, voltage-gated sodium channels play a key role in the propagation of excitation along the nerve fiber. In peripheral neurons, sodium channels types 1.7, 1.8 and 1.9 are predominantly expressed. They have different kinetics, exhibit slightly different expression patterns, and are all related to the pathophysiology of pain. Channels 1.7 can generate action potentials in response to slow depolarization [17] and thus determine the threshold for nociceptor activation. Channels 1.8 are necessary for the transmission of pain information, since they carry most of the charge during the depolarizing phase of the action potential in dorsal ganglia neurons [18, 19] and are involved in the generation of repeated neuronal discharges. Channels 1.9 are characterized by slow kinetics and are capable of generating constant charges at potentials close to the membrane resting state, which emphasizes their importance as regulators of cell membrane excitability [20–22]. There are also voltage-gated potassium channels, in particular HCN2, which cause hyperpolarization of the membrane and reduce the excitability of afferents [23]. This type of channel is thought to act as a pacemaker, modulating ectopic activity caused by nerve damage.

Regulation of ion channel activity

Nociceptors can change the state of ligand-associated and voltage-gated ion channels under the influence of various signals. Such regulation includes changing the degree of activity of the channels themselves, for example, through their phosphorylation or binding to various modulators, transfer of channels from the intracellular space to the membrane surface (trafficking) and regulation of transcription. The results of experimental and clinical studies indicate that the occurrence of NB is a consequence of damage to afferent pathways. It has been shown that when a peripheral nerve is damaged, spontaneous activity is generated both in the affected and in neighboring intact nociceptive afferents [24, 25]. The possibility of ectopic activity is correlated with increased levels of trafficking and expression of TRPV1 [26-28], as well as the expression of voltage-gated sodium channels [29-31] in neighboring nociceptors. Increased expression of TRPV1 receptors can lead to spontaneous neuronal activity at normal body temperature if the activation threshold of the TRPV receptor falls below 37oC [32]. Clinically, it is characterized by temperature hyperalgesia and the presence of constant burning pain [33].

Animal models of nerve damage have shown that many mediators acting at the level of intracellular signaling pathways can coordinate the cellular response to nerve damage and directly influence the transmitting properties of nociceptive afferent axons, causing their constant activity [34]. For example, protons can both directly activate TRPV1 and reduce the threshold for their activation [35, 36]. The entry of calcium ions into the cell through TRPV1 and their release from cellular stores activate the phosphorylation processes of these receptors due to the influence of calcium-calmodulin-dependent protein kinase [37]. Prostaglandins E2 and I2 also influence the activation threshold of TRPV1 in the sequence receptor - G-protein - protein kinase - A-dependent pathway - TRPV1 [38, 39]. The effects of other mediators such as bradykinin, ATP and endothelin-1 are associated with interaction with G-protein-associated receptors and the diacylglycerol-protein kinase C system [40]. These mechanisms increase the phosphorylation level of TRPV1. On the other hand, phosphatases such as calcineurin and protein phosphatases 2A and 2B cause neuronal desensitization and increase the activation threshold of TRPV1, thus preventing the spread of pain impulses [41, 42], which is achieved by dephosphorylation under the influence of calcium ions [43, 44]. Thus, TRPV1 activity may be determined by the phosphorylation state of TRPV1 channels.

Another mechanism for modulating the activity of TRPV1 channels is the regulation of the number of receptors on the neuron membrane through trafficking from the intracellular space and synthesis of receptors. This regulatory mechanism can be carried out under the influence of a number of cytokines, in particular interleukin 1β, tumor necrosis factor alpha (TNFα) and nerve growth factor (NGF) [45, 46]. The main producers of cytokines during nerve damage are cells of the immune system (macrophages, neutrophils and T-lymphocytes) migrating to the spinal ganglia, and activated microglial cells [47-49]. Animal models of nerve injury and clinical settings have shown increased concentrations of TNFα, interleukin-1, and NGF in injured nerves [50–52]. Injection of TNFα into the nerve causes hypersensitivity to pain in rats, and inhibition of the influence of TNFα reduces pain hyperesthesia in response to mechanical stimulation [53–55]. The influence of NGF on the expression of TRPV1 on nociceptors through tyrosine kinase receptors type A (TrkA) has also been established [52]. The latter are characterized by a high level of expression on pain afferents [56]. Another mechanism of nociceptor sensitization has been established, associated with an increase in the retrograde transport of NGF to the cell body [57]. Thus, damage to some neurons and, accordingly, loss of trophic support by them leads to an increased influence of growth factors on others, causing their sensitization [58].

Other mechanisms of sensitization have also been described, in particular the connection of this phenomenon with the activation of toll receptors on sensory neurons [59], as well as the adrenergic effect of sympathetic nerve fibers due to the sprouting of the latter in the spinal ganglia [60]. A number of receptor-associated proteins and compounds, in particular phosphatidylinositol 4,5 biphosphate (PIP2) and some cytoskeletal components, also play a significant role in modulating TRPV1 activity. Experimentally, PIP2 has been shown to increase temperature hypersensitivity and allodynia in response to mechanical stimuli in models of inflammation and nerve damage [61]. Activation of TRPV1 affects the state of the cytoskeleton; for example, it can cause rapid dissociation of microtubules and, thus, lead to the elimination of sensory afferents from the epidermis [62]. In addition, it was shown that TRPV1 is usually localized near growth centers and ends of filopodia, which indicates the participation of the receptor in the regulation of the morphology and functions of these structures, and, consequently, in the provision of interneuron connections [62].

Thus, many mechanisms for the development of NB have been described, the central element of which is an increase in the activity of TRPV1 receptors. It is assumed that these receptors play the role of integrators of various molecular signals about the presence of damage and inflammation [28]. In this case, receptors are involved not only in the transmission of pain stimuli, but also in regulating the functioning of the neural network responsible for the formation of pain syndrome [63]. It should be noted that a significant part of the experimental and clinical data was obtained through the use of a highly selective TRPV1 receptor ligand, capsaicin, which was used as a tool to provoke NB.

Capsaicin

Capsaicin is the substance responsible for the fiery, spicy taste of chili peppers ( Capsicum frutescens

), which is widely used in cooking. Capsaicin and several other molecules of this type are known collectively as capsaicinoids, and they are produced by all plants of the capsaicin family except white pepper. Medicines containing capsaicin are popular in traditional medicine for the treatment of pain syndromes. The analgesic effects of capsaicin were initially thought to be due to increases in local perfusion and temperature and “capsaicin pain,” which suppresses other noxious stimuli [37]. Cloning of the capsaicin receptor, TRPV1, has opened the way to investigation of the molecular mechanisms of capsaicin's various effects.

TRPV1 was found both on skin nociceptors and on neurons of some parts of the central nervous system [63], astrocytes [64], Schwann cells, mast cells [65], vascular myocytes, bronchial epithelial cells [66], keratinocytes [67], nerve fibers of the gastrointestinal tract [68-70]. This indicates a wide range of functions of the TRPV1 receptor and, therefore, multiple effects of capsaicin on different physiological systems. The participation of TRPV1 in the regulation of the tone of blood vessels, bronchi, muscles of the gastrointestinal tract and bladder, the implementation of the cough reflex, the perception of hunger, body temperature, and pain signals has been described [37, 71].

When capsaicin is applied to the skin in the form of a cream, ointment or patch, it is rapidly absorbed and acts almost exclusively at the local level, due to the low penetration of capsaicin into the systemic circulation and its very short half-life. Thus, the highest concentration of capsaicin in blood plasma after the use of 8% capsaicin in a dermal patch (cutenza) in clinical studies was 17.8 ng/ml [72]. For comparison, when consuming 5 g of chili pepper (equivalent to 26.6 mg of pure capsaicin), its peak plasma concentration was 2.47 ± 0.13 ng/ml [73]. There is evidence that the average daily consumption of pepper in Mexico is about 20 g per person [74]. The mean half-life of capsaicin in clinical studies was 1.64 hours. The mean area under the concentration curve and the mean peak concentration of capsaicin after 60-minute application of the dermal patch were 7.42 ng/ml·h and 1.86 ng/ml, respectively [72]. . The synthetic trans-capsaicin used in the dermal patch biotransforms slowly in human skin, and most capsaicin remains unchanged when applied topically. A small fraction of it is converted into vanillylamine and vanillic acid.

Studies on various animal species have shown that cutenza does not have mutagenic or teratogenic effects.

Capsaicin has been widely used in animal experiments and in studies on healthy volunteers to study the mechanisms of transmission and modulation of pain signals. Long-term stimulation of peripheral C- and Aδ-fibers when injecting capsaicin or applying it to large areas of skin triggers mechanisms of temporary summation, central sensitization and long-term potentiation [75]. Application of capsaicin to the skin or intradermal administration provokes acute burning pain, hypersensitivity to temperature and mechanical stimuli, and allodynia of the surrounding areas of the skin [76-79]. The binding of capsaicin to the TRPV1 receptor, in addition to causing pain involving the previously described mechanisms, causes local neurogenic inflammation caused by the exocytosis of substance P from nociceptors, which leads to degranulation of mast cells and the release of histamine and serotonin from platelets [76, 80]. However, the effects of capsaicin can vary significantly depending on the dose and duration of application. Thus, in 1977 [81], it was shown that the use of capsaicin can lead to long-term loss of sensitivity to pain caused by mechanical stimuli. When capsaicin was administered intravenously to newborn rats in doses exceeding therapeutic doses, not only desensitization of sensory afferents was detected, but also degeneration of sensory neurons in the spinal ganglia [82]. Repeated applications of 1% capsaicin cream over several weeks reduced pain response to both thermal and mechanical stimuli [83, 84]. Thus, it has been shown that a single local application of capsaicin in a low concentration causes sensitization of nociceptors, while its repeated local application in low concentrations or a single application in a high dose leads to a decrease in pain sensitivity [76, 77, 85].

The process of desensitization when using capsaicin in high doses develops in several stages [37]. The first stage takes approximately 20 s and includes binding of the agonist to TRPV1, increased entry of Ca2+ ions and activation of a number of enzymes, in particular calcineurin, which dephosphorylate TRPV1 [43, 76, 86]. In addition, voltage-gated ion channels are inactivated, which also leads to rapid desensitization, since new action potentials cannot be generated [76, 87]. It is believed that desensitization of nerve fibers is a protective mechanism that prevents excessive calcium influx into neurons, which can lead to their excitotoxic death [37]. These effects were recorded simultaneously with the development of neurogenic inflammation.

The next stage takes approximately 72 h and involves the degeneration of nociceptive fibers in the epidermis, and such degeneration affects only those fibers that were in direct contact with capsaicin [76]. This fiber disappearance may be due to previously described microtubule rearrangement or mitochondrial dysfunction [88]. Capsaicin-induced reductions in nociceptor density have been demonstrated in human skin biopsies using immunostaining techniques [85]. Application of a cream with a low concentration (0.075%) of capsaicin 4 times a day for 3 weeks led to a significant decrease in nociceptor density [83]. After a single application of cutenza in healthy volunteers, the density of nociceptors decreased by 80% after 1 week, there was a slight (8%) increase in the threshold of tactile sensitivity and a decrease in pain in response to mechanical irritation (by 15%) [86-89]. At the same time, the thresholds of sensitivity to heat and cold did not change [86].

The decrease in nociceptor density after capsaicin administration is reversible. The time required for reinnervation and restoration of nociceptor function depends on the degree of neurite degeneration caused by capsaicin administration. When capsaicin was stopped, the number of nociceptors recovered within 6 weeks [90]. Regeneration was accompanied by restoration of skin sensitivity to painful stimuli [83]. After a single application of cutenza, restoration of the initial density of nociceptors occurred within 24 weeks, which was combined with a more prolonged analgesic effect [85].

Thus, the results of experimental studies have shown that capsaicin exhibits different properties, even diametrically opposed ones, depending on the concentration and duration of use. One of these properties, namely the long-term reduction in pain sensitivity after a single application of a high dose of capsaicin, provides unique opportunities for the clinical use of this drug.

Results of clinical trials of cutenza

Qutenza is an innovative dermal system containing capsaicin at a concentration of 8% and optimized for rapid absorption of the drug into the skin. Previous attempts to use capsaicin in high concentrations were limited by the severe pain reaction and unpleasant irritant effect of pepper spray on both the patient and the physician.

In one study using 7.5% capsaicin cream in patients with HIV-associated neuropathy (HIV-AN), epidural anesthesia was necessary to tolerate the application [91]. The use of the cutenza patch, especially in combination with a local or systemic analgesic, can minimize pain and irritating odor.

Qutenza is approved in the European Union for the treatment of patients with peripheral NP who do not have diabetes mellitus, and in the USA for the treatment of PHN [92, 93]. Recommendations for the use of cutenza have a substantial evidence base. Brief characteristics of published phase II and III clinical studies are presented in Table. 2

[94-109].

www.clinicaltrials.gov lists at least 10 other studies of cutenza, including 2 completed phase III clinical trials in patients with painful diabetic polyneuropathy, 2 completed phase IV studies (comparing the effectiveness of cutenza and pregabalin and comparing the effectiveness of tramadol and lidocaine before application of cutenza) and 1 ongoing phase IV study of repeated applications of cutenza for peripheral NP.
In 2013, a meta-analysis of 7 completed randomized, double-blind controlled trials was published [6] and a Cochrane review of topical capsaicin in the treatment of chronic NP in adults [110]. The main diseases for which the effectiveness of cutenza has been studied are PHN, HIV-AN polyneuropathy. There are anecdotal reports of studies of cutenza in phantom pain, peripheral polyneuropathy in patients with chronic renal failure, chronic pain associated with arteriovenous fistula [75,98] and trigeminal neuralgia [111].

The design of most phase II and III clinical trials was similar. These were multicenter, randomized, double-blind, controlled studies of 12 weeks duration. The exceptions are the 4-week study C102 and multicenter open-label extension studies - C106, C 108, C114, C118 (see Table 2)

. Patients in the comparison group received a 0.04% capsaicin patch to maintain blinding, since a real placebo would not cause the application site reaction that occurs with cutenza. The primary method for assessing effect was the percentage change in patient pain perception (average pain intensity rating over the past 24 hours). An 11-point numerical rating scale was used, according to which 0 points is the absence of pain, and 10 points is the most intense pain. Pain intensity scores at baseline were compared with pain intensity scores at weeks 2–8 in the PHN studies and weeks 2–12 in the HIV-AN studies. Week 1 data were not included in the analysis because patients may have received opioids to reduce pain caused by the patch.

Secondary efficacy measures were the percentage of patients with greater than 30% and 50% pain reduction and greater than 2 NPRS pain relief from baseline. This assessment was also performed at weeks 2 and 12 in PHN studies. Other scales and questionnaires have been used to more broadly assess the effect of cutenza on the quality of life of patients. Another criterion for the effectiveness of treatment in a number of studies was the concomitant use of drugs to relieve NB. Thus, in study C116, 50% of patients received concomitant medications; in a phase III study of PHN, such patients accounted for 22% [101, 106].

The use of cutenza has been associated with local skin reactions such as irritation, redness and burning pain at the site of application. These effects were transient and mild to moderate in intensity [112–114]. Local cooling and application of anesthetics and opiates have been used successfully to control this reaction. When using cutenza, there were no side effects from the central nervous system such as drowsiness or dizziness, and there is no data on the development of neurological disorders in patients with NB after using cutenza.

A meta-analysis was conducted of 7 randomized, double-blind, controlled trials involving 1313 patients with PHN and 801 patients with HIV-AN [6]. According to the analysis, on average, 43% of patients (44% with PHN and 41% with HIV-AN) had a clinically significant effect (reduction of pain by more than 30% compared to baseline) within 3 months after application. In 11 and 7% of patients with PHN and HIV-AN, respectively, there was complete regression of pain from the 2nd to the 12th week of observation. The onset of effect in patients with PHN was observed on average 3-4 days, and in patients with HIV-AN - 5-6 days after the use of cutenza. This duration of onset of therapeutic action approximately corresponds to the onset of action of other drugs used to treat NB, used in therapeutic doses (without taking into account the dose titration period) [6]. At 1-year follow-up, 40% of patients with PHN and 36% of patients with HIV-AN enrolled in the clinical expansion trial experienced a greater than 30% reduction in NB intensity. In 9% of patients with PHN and 10% of HIV-AN patients, complete regression of pain was recorded from the 2nd week to the end of the observation period. To maintain a long-term effect, approximately 2/3 of patients (74%) required only 1-2 patch applications.

A reliable criterion for assessing the effectiveness of treatment is the NNT (numbers needed to treat) indicator - the number of patients who must receive the drug in order to record the effect in one patient compared to the control. For cutenza, this indicator ranges from 6 to 9 when assessing the condition of patients after 8 or 12 weeks from the start of treatment, respectively [110]. These results can be compared with data from clinical studies of other treatments for NB. In a study of pregabalin 600 mg in 702 patients with PHN, the NNT after 12 weeks of treatment was 5.4 (range 3.9 to 9.2) [115]. The NNT for detecting a good and very good therapeutic effect of gabapentin used in randomized clinical trials (a total of 1121 patients included) was 5.5 (range 4.3 to 7.7) [114, 115]. The review authors concluded that the improvement achieved with cutenza is comparable to that of other drugs for the treatment of NB [110]. Although not all patients experienced improvement, those patients who reported significant pain relief also reported relief from fatigue, decreased depression, and improved sleep and quality of life. A multicenter, open-label, randomized study of the comparative efficacy and safety of cutenza and pregabalin, ELEVATE, in 568 patients with peripheral NP showed that cutenza was noninferior to pregabalin over 8 weeks of follow-up. The effect of cutenza was even superior to pregabalin in terms of the reduction in numerical pain rating scale scores in absolute terms from weeks 1 to 3 and in average values ​​at all measurement points (from weeks 2 to 8) [116].

Thus, clinical studies of the use of cutenza have shown an acceptable safety profile of the drug and effectiveness comparable to other drugs for the treatment of NB. Clinically significant pain relief was achieved in approximately 43% of patients, with 7-11% of patients experiencing complete pain relief. In cases where a clinically significant effect of cutenza was observed, it persisted for at least 3 months and was reproduced with repeated applications of the drug.

Conclusion

A review of the peripheral mechanisms of NB development showed that capsaicin receptors TRPV1 play a key role as integrators of various high-threshold chemical and temperature signals. There is a complex and multi-level system for regulating the activity of these receptors. Regulatory signals, including capsaicin, can both provoke NB and cause “defunctionalization” of sensory afferents. The latter phenomenon was used in clinical practice thanks to the development of an innovative dermal system of high-dose capsaicin cutensis, which allows minimizing the pain reaction and irritating effect of capsaicin aerosol on the mucous membranes. Clinical studies have shown that the effectiveness of a single application of cutenza is not inferior to the pain relief achieved by taking other drugs, and the duration of the effect exceeds 3 months. Qutenza does not act at the systemic level and is devoid of such negative characteristics as adverse reactions from the central nervous system, drug interactions and the need for long-term dose titration, characteristic of oral drugs for the treatment of NB. The drug is effective both as monotherapy and as part of rational multimodal polypharmacotherapy. Evaluation of the effectiveness of the patch showed a decrease in the severity of depression, asthenia, improvement in sleep and quality of life. However, clinically significant improvement (reduction in pain intensity by at least 30%) was not observed in all patients.

In fact, such selectivity of action is a common phenomenon for all drugs for treating NB [11]. Analysis of clinical studies of cutensis allowed us to identify a number of subgroups of patients with diabetic polyneuropathy [118] and postherpetic neuralgia [119] with different responses to treatment. However, the clinical significance of identifying subgroups for predicting the effectiveness of therapy has not yet been determined. To date, specific biomarkers have not yet been proposed to identify individual pain mechanisms. Characteristics such as pain intensity, etiology, or pain type do not appear to be predictors of response to treatment [118, 120]. The solution may be to compile an individual profile of sensory disorders [118, 120]. Several studies have already been published in which the identification of subgroups of patients taking into account the individual characteristics of sensory disorders has yielded encouraging results [120–128]. But until scientific research provides clear recommendations on how to identify such patients, the only possibility is to observe the effect after using cutenza.

Capsaicin ointment for joints: a review of the best drugs

Medicines with a warming and analgesic effect are actively used in the treatment of joint diseases. Among the best ointments with capsaicin for joints it should be noted:

Athletes use Nicoflex ointment

1. Nicoflex ointment. Most often prescribed for the treatment of arthritis and arthrosis. In addition to relieving pain, it relieves inflammation and helps increase joint mobility. The drug can be used by people of any age (except children). The average course of treatment is no more than 5 days.
2. Camphocin. Helps with rheumatism and arthritis. When applied, it has a double warming effect. Quickly relieves signs of inflammatory processes.
3. Rescuer Forte. Helps restore joint function and tissue regeneration. It is popular among professional athletes, as it quickly helps with sprains, dislocations, bruises and other injuries. Noticeable relief occurs 5-7 minutes after rubbing into the skin. The duration of action lasts for several hours.
4. Capsicum ointment. It has an antibacterial, anti-inflammatory, antioxidant and warming effect on sore joints. When applied, it causes a noticeable tingling and burning sensation. The duration of treatment is individual in each case.

The effect of the balm “Rescuer Forte”
Any of them will not be difficult to buy at the pharmacy. If it is impossible to use one, you can always turn to the help of an equally worthy analogue (cream or gel) with the same active ingredient - capsaicin.

Capsaicin analogues

Analogs of ointment with capsaicin include any drugs that have a similar warming effect. However, they may contain other active ingredients.

Ointments with a warming effect Possible analogues:

• Apisatron
• Sophia
• 911
• Viprosal
• Finalgon

Gum turpentine, snake venom and turpentine oil have a warming effect. If you find them in creams, you can buy them as analogues of products containing capsaicin.