A Review on the role of Capsaicin in Neuropathic Pain
Abhishek Chaudhary, Divya Arora*, Pooja Devi
Abhilashi University, Chail Chowk, Tehsil Chachyot, Mandi, Himachal Pradesh - 175028, India.
*Corresponding Author E-mail: dvarora50@gmail.com
ABSTRACT:
As we know, there is tremendous cases of neuropathic pain seen recently in the world. Due to the toxic effects of drugs used to reduce this severe dysfunction, one can always move towards the herbal products or substances available in nature. Nature has numerous drugs that can be used to cure even severe diseases. One of which is Capsaicin which is available in the Capsicum or pepper. This Capsaicin plays a vital role in the treatment of neuropathic pain. In this article, we will discuss the roles and importance of Capsaicin (Pepper) found in Capsicum in neuropathic pain.
Figure 1: Structure of Capsaicin
Capsaicin (CAP) is a compound found in almost all types of peppers, responsible for their characteristic pungent aroma. CAP was first described in 1816 by Christian Bucholz and its chemical composition, 8-methyl-N-vanillyl-6-nonenamide, was revealed in 1919 2. vanilloid subtype 1 (TRPV1) found on A- and C-delta fibers in the nociceptive sensory pathway, which initiates the signal transduction cascade that finally leads to desensitization of the afferent nerve fibers2,3.
CAP binds to a transient receptor potential channel of CAP from the berries of Capsicum species is among the most widespread spices used in cuisines throughout the world 4, and harbors many benefits that have extensively been documented in various in vivo, ex vivo, and in vitro studies. CAP and the related nonpungent capsinoids (capsiate, dihydrocapsiate, nordihydrocapsiate) have been proven to elicit analgesic, antioxidant, anti-inflammatory, anticarcinogenic, weight modulatory, cardio-protective, anti-lithogenic, and circadian-modulatory effects5. Therefore, besides its culinary utilization, CAP has been used as a therapeutic agent in various painful chronic conditions, such as those encountered in diabetic and nondiabetic neuropathy, temporo-mandibular joint disorder, burning mouth syndrome, postherpetic neuralgia, osteoarthritis, or rheumatoid arthritis2,6–8. On the other hand, there are data showing that chronic exposure to high doses of CAP can enhance the development of liver, stomach, duodenal, and prostate cancer, and can induce peptic ulcers2,9,10. Even if several adverse effects have been described on common doses, CAP has no absolute contraindication, and only a few relative contraindications, such as asthma. The antidote is still unknown, but there were no reported overdoses of any preparation of capsaicin2. Moreover, one prospective study noted that subjects who consumed spicy food almost daily had a 14% lower risk of death, without being able to make a causal relationship11. Changing the biodiversity of gut flora has been associated with a high risk of autoimmune and allergic diseases, obesity, inflammatory bowel disease (IBD), diabetes, cancer, cardiovascular diseases, and cirrhosis12–21. Thus, remodeling the gut microbiome by dietary supplements or food additives could represent an innovative therapeutic strategy against various diseases. Spicy food, especially CAP, recently drew considerable attention from the perspective of their positive action on gut flora, by eliminating the disease-causing enteric pathogens, and encouraging the growth of beneficial bacteria22–24. However, due to frequent consumption and its therapeutic valence, a comprehensive assessment of CAP effects is an important goal from the public health standpoint9.
Neuropathic Pain: Who is at Risk?
Around 5 percent of the population is thought to be affected by neuropathic pain (NeP). Mechanistically targeting a neuropathic patient's pain, on the other hand, is frequently fruitless, and many patients do not achieve appropriate analgesia from their pain treatment regimen (25, 26). The Doleur Neuropathique 4 questionnaire, sometimes known as the DN4, is a screening tool for determining the likelihood of peripheral or central neuropathy as a symptom of severe pain (27). Age (middle age, 50–64 years), gender (the prevalence of chronic pain is higher in women), specific site of damage (monoor polyneuropathies can emerge in different anatomical regions), and sociodemographic status are all risk factors that might lead to the development of NeP (28– 30). Individuals' genetic backgrounds can predispose or prevent them from developing NeP31, and a sufferer's emotional and cognitive well-being influence how they respond to chronic pain.The issue is confusing in general. As a result, the capacity to completely appreciate the genuine epidemiological facts and data about NeP incidence is hampered, and the disease's prevalence is unquestionably underestimated32.
Role of Capsaicin in Neuropathic Pain:
Topical capsaicin has been marketed in a variety of doses and formulations, including gels, creams, sprays, and patches, since its medicinal introduction in the mid-19th century. During early development, topical capsaicin formulas comprised low dosages (1 percent) and required frequent and continuous administration for long periods of time, such as 3 or 4 applications daily for a minimum of six weeks33. Despite this, investigations on the efficacy of low capsaicin concentrations in the treatment of chronic pain have come up with mixed results34. Capsaicin's utility as an analgesic was substantially boosted by the creation of patches with a high concentration of capsaicin (8 percent) (Qutenza, created by NeurogesX and presently is supplied by Grünenthal)35. The therapeutic utility of Qutenza for chronicpain treatment has been extensively reviewed previously36-39. Compared to a 0.4 percent capsaicin control patch, Qutenza produces long-lasting analgesia for self-reported pain in patients with post-herpetic neuralgia (PHN). Analgesia lasts for three months after a single 60-minute application, and the patient can be treated again every three months. Capsaicin absorption is limited after topical application of Qutenza, and elimination is quick, with a half-life of 1.6 hours40. Capsaicin is processed in the liver by numerous cytochrome P450 enzymes41. Capsaicin does neither activate or inhibit cytochrome P450 enzymes in the liver in the range of systemic concentrations attained after topical treatment (58nM) and is unlikely to alter medication metabolism. As a result, topical capsaicin has demonstrated no medication interactions and can be used safely alongside other regularly used analgesics. Topical capsaicin has only minor side effects, the most prevalent of which are a brief temporary increase in blood pressure and local reactions at the application site, such as searing pain, erythema, and itch. During the 52 weeks observation period, patients tolerated repeated treatments well. Nonetheless, because capsaicin metabolism in skin is slow and capsaicin has been claimed to have carcinogenic potential, the repeated injection of capsaicin aroused concerns. Furthermore, capsaicin's carcinogenic potential appears to be linked to impurities in capsaicin extracts, and there is no evidence for carcinogenic consequences of pure capsaicin. Furthermore, the anti-cancer properties of capsaicin are more well-established42. Qutenza was licenced by the US Food and Drug Administration in 2009 for the treatment of neuropathic pain associated with PHN, and in 2020 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy, based on these therapeutic efficacy and safety results. Qutenza has been licenced in the European Union for the treatment of peripheral neuropathic pain in adults, both alone and in combination with other pain medications. Capsaicin compositions in different forms are currently being researched. Centrexion's CNTX-4975 is an injectable capsaicin used to treat Morton's neuroma and pain from osteoarthritis of the knee. Propella Therapeutics is also working on a liquid form of high-concentration capsaicin (CGS-200) to treat painful knee joint osteoarthritis43.
CONCLUSION:
The present review article focusses on explain the role of Capsaicin in Neuropathic pain. To understand this, one should first understand what is the Neuropathic pain. Then, it is important to understand the composition of Capsaicin and it’ s presence in Pepper or Capsicum. Very few drugs are available which helps to reduce the Neuropathic pain. Also, they have severe side effects, which can be avoided if the use of herbal products is done. So, here comes the Capsaicin showing the equivalent effects in Neuropathic pain with minimal side effects.
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Received on 02.04.2022 Modified on 30.06.2022
Accepted on 23.09.2022 ©AJRC All right reserved
Asian J. Research Chem. 2022; 15(6):495-498.