It consists of refined and standardized capsicum oleoresin, containing between 12-18% of total capsaicinoids, expressed as capsaicin. The oleoresin is obtained using ethanol (minimum 90% v/v).
Capsicum oleoresin is an oily organic resin derived from the fruit of plants in the Capsicum genus, such as hot peppers. When the plants are finely ground, capsicum oleoresin is formed after the capsaicin extraction process using organic solvents. It is commonly used as a culinary spice. The intensity of the biological actions of capsicum oleoresin are a direct function of the amount of capsaicinoids, or capsaicin, present in compound6. Capsaicinoids are part of a group of fat-soluble pungent chemical phenols and include capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin3. Capsaicin and dihydrocapsaicin are the hottest capsaicinoid analogues 3.
Capsicum oleoresin is found in pepper sprays when suspended in water and acts as an active lachrymatory agent, inducing irritation, tearing, pain and temporary blindness when in contact with the eyes. Due to its analgesic properties, oleoresin capsicum is used to temporarily relieve minor muscle and joint pain as an active ingredient in over-the-counter topical preparations and has been studied for the treatment of different models of neuropathic pain1. It is suggested that oleoresin de capsicum is a rich source of phytochemicals consisting of phenolic compounds with antioxidant and antidiabetic activities 2.
Elements that make up the oleoresin of capsicum in addition to capsaicin (8-methyl-N-vanillyl-6-nonenamide):
Dihydrocapsaicin, norhydrocapsaicin, and homocapsaicin. It also contains carotenoids such as capsanthin and capsorubin, and flavonoids such as apioside and lutein. In addition, it contains copper and vitamins B1, B2, and C.
Capsicum oleoresin is a topical analgesic and inflammatory agent.
Capsaicin, an active ingredient in capsicum oleoresin, causes pain and sensitization of the peripheral and central nerves. It induces primary and secondary hyperalgesia and mimics the symptoms associated with neuropathic pain, such as allodynia, secondary hyperalgesia, area of referred pain, and viscerovisceral hyperalgesia4.
Conversely, capsaicin also mediates analgesic actions through desensitization and withdrawal of epidermal nerve fibers4. Systemic reviews of capsaicin-containing topical formulations demonstrate clinical efficacy for pain reduction in post-herpetic neuralgia , post-surgical neuropathies and diabetic neuropathy, compared with placebo 1.
Mechanism of action 7:
Capsaicin acts as a highly selective agonist of the transient receptor potential V1, also known as TRPV1 (transient receptor potential cation channel), which is a non-selective cation channel. Its high selectivity is due to the fact that it does not agonize other homologous channels of the TRPV receptor family.
It acts as a polymodal receptor, being activated by a wide range of harmful stimuli, whether physical, thermal or chemical (for example, pH); although it presents greater sensitivity to capsaicin (as an exogenous activator) (Yang & Zheng, 2017).
TRPV1 was discovered in 1997 by cloning dorsal root ganglia expressed in human embryonic kidney cells (Christie et al., 2018). The initial discovery of the receptor stimulated interest in exploring the therapeutic benefits that capsaicin can provide (Basith et al., 2016).
Regarding the structure of the TRPV1 channel, it consists of 4 identical subunits, located in the plasma membrane of tissue cells. For its part, each receptor subunit* consists of an N-terminal (part A), a transmembrane region (part B) and a C-terminal (part C). In the transmembrane region we find 6 helical segments (S1-S6), where S1-S4 corresponds to the voltage-sensing domain, and S5-S6 contributes to the pore-forming domain. The S1-S4 domain is linked to the S5-S6 domain by a link that allows the opening of the pore and the activation of TRPV1. helical s –- S6 contributes to S6 through a bond In this transmembrane region there are binding sites for different ligands, including capsaicin (Christie et al., 2018). Figure 4: Structure of a TRPV1 subunit (Christie et al., 2018).
Regarding the interaction of capsaicin with the receptor, region A and region C of the chemical structure of capsaicin* form hydrogen and Wan der Waals bonds with TRPV1, respectively (Yang & Zheng, 2017).
TRPV1 is expressed centrally (highly in the brainstem, midbrain, hypothalamus, and limbic system) and peripherally (in the vagus and spinal nerve, stomach, and adipose tissue) (Christie et al., 2018). It is mainly located in C fibers of afferent neurons and in some Aδ fibers (Groninger & Schisle r, 2012).
When the receptor is activated by capsaicin, there is an increase in membrane permeability to cations, sodium and calcium ions flow through the receptor, giving rise to a firing action potential (Yang & Zheng, 2017). This leads to nerve depolarization which, after spreading to the spinal cord and brain, produces the local heat, stinging, and/or prickling sensation characteristic of this active principle (Groninger & Schisler, 2012).
It is worth noting the intervention of the neuropeptide substance P as a mediator of the transmission of painful impulses (Figure above), from nociceptive neurons to the CNS (Vidal et al., 2004). The repetitive activation of TRPV1 receptors by capsaicin causes axoplasmic transport blockade of substance P and other neuropeptides such as somatostatin. This blockade results in the reduction of these neuropeptides, which was thought to be the main pathway through which the analgesic effect was produced (Sharma et al., 2013).
Currently, it is known that the repeated topical use of capsaicin can cause, at the molecular level, a conformational change of TRPV1, which leads to the closure of the channel. After a cascade of events, we can say that the neuron begins a reversible refractory period, in which it becomes insensitive to different stimuli, whether endogenous or exogenous. This situation is called defunctionalization or desensitization (Sharma et al., 2013).
- Groninger H, Schisler RE: Topical capsaicin for neuropathic pain #255. J Palliat Med. 2012 Aug;15(8):946-7. doi: 10.1089/jpm.2012.9571.
- Sricharoen P, Lamaiphan N, Patthawaro P, Limchoowong N, Techawongstien S, Chanthai S: Phytochemicals in Capsicum oleoresin from different varieties of hot chilli peppers with their antidiabetic and antioxidant activities due to some phenolic compounds. Ultrason Sonochem. 2017 Sep;38:629-639. doi: 10.1016/j.ultsonch.2016.08.018. Epub 2016 Aug 12.
- Yeung MF, Tang WY: Clinicopathological effects of pepper (oleoresin capsicum) spray. Hong Kong Med J. 2015 Dec;21(6):542-52. doi: 10.12809/hkmj154691. Epub 2015 Nov 6.
- O’Neill J, Brock C, Olesen AE, Andresen T, Nilsson M, Dickenson AH: Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev. 2012 Oct;64(4):939-71. doi: 10.1124/pr.112.006163.
- Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA: Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. Molecules. 2016 Jun 28;21(7). pii: molecules21070844. doi: 10.3390/molecules21070844.
- Oleoresin Capsicum Toxicology Evaluation and Hazard Review
- Potencial terapéutico de la Capsaicina. David Cano Pérez. UNIVERSIDAD DE SEVILLA. Facultad de Farmacia.