Role of trpv1 (transient receptor potential v1 channel) in piperine induced hyperalgesia: a preliminary study

  • Authors

    • Priyanshee Gohil Department of Pharmacology and Clinical Pharmacy, K.B. Institute of Pharmaceutical Education and Research, Kadi Sarvavishvawidyalaya, Gandhinagar, Gujarat, India.
    • Gaurang Shah Department of Pharmacology and Clinical Pharmacy, K.B. Institute of Pharmaceutical Education and Research, Kadi Sarvavishvawidyalaya, Gandhinagar, Gujarat, India.
    • Chhaya Patel Department of Pharmacology and Clinical Pharmacy, K.B. Institute of Pharmaceutical Education and Research, Kadi Sarvavishvawidyalaya, Gandhinagar, Gujarat, India.
    2014-10-17
    https://doi.org/10.14419/ijpt.v2i2.3269

  • Background: The inflammatory disease is associated with chronic pain and hypersensitivity to noxious stimuli in form of hyperalgesia. Transient receptor potential vanilloid type-1 (TRPV1) activated by various inflammatory mediators; plays a key role in occurrence of hyperalgesia. Piperine is the primary pungent alkaloid of Piper nigrum. Piperine has common binding site with capsaicin (TRPV1 agonist) on TRPV1 and it has more efficacy for activation of TRPV1 than capsaicin.

    Objective: The purpose of the study was to investigate the role of TRPV1 in piperine induced hyperalgesia in diabetic mice.

    Methods: Diabetes mellitus was induced in mice using streptozotocin (STZ). Nociception was measured by three types of thermal nociceptive tests (Hot plate method, radient heat tail-flick method and tail immersion test). Pilot study (using 2.5, 5, 10 and 50 mg kg-1 piperine, i.p.) was carried out and 5 mg kg-1 piperine is used as optimum dose for further study. Capsaicin, capsazepine and piperine were administered to their respected groups and nociceptive threshold was noted on day 4, 7 and 10 in all groups.

    Results: Piperine showed a significant decrease in nociceptive threshold as compared to diabetic control group, while there was a significant increase in reaction time, tail flick latency and tail withdrawal latency, in the animals pre-treated with capsazepine before piperine administration as compare to only piperine treated diabetic group.

    Conclusion: Activation of TRPV1 might be one of the possible mechanisms of Piperine induced hyperalgesia.

    Keywords: Capsaicin, Capsazepine, Hyperalgesia, Nociceptive Threshold, Piperine, TRPV1.

  • References

    1. Arpad S (2005) Piperine: Researchers discover new flavor in an ancient spice. Trends in Pharmacological Sciences 26(9), 123-126.
    2. Bevan S, Hothi S, Hughes G, James IF, Rang HP & Shah K (1992) Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. British Journal of Pharmacology 107, 544-552. http://dx.doi.org/10.1111/j.1476-5381.1992.tb12781.x.
    3. Bichoy H & Pierr S (2003) Kinin B1 receptor antagonists inhibit diabetes-induced hyperalgesia in mice. Neuropeptides 37, 36-44. http://dx.doi.org/10.1016/S0143-4179 (02)00148-8.
    4. Caterina MJ, Leffler a & Malmberg AB (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, 306-313. http://dx.doi.org/10.1126/science.288.5464.306.
    5. Caterina MJ, Schumacher MA, Timinaga M, Rosen TA, Levine JD & Julius D (1997) The capsaicin receptor:a heat-activated ion channel in the pain pathway. Nature 389, 816-824. http://dx.doi.org/10.1038/39807.
    6. Cesare P, Moriondo A, Vellani V & McNaughton PA (1999) Ion channels gated by heat. Proceedings of the National Academy of Sciences of the United States of America 96, 7658-7663. http://dx.doi.org/10.1073/pnas.96.14.7658.
    7. Chakir M & Plante GE (1996) endothelial dysfunction in diabetes mellitus. Prostaglandins Leukotrienes and Essential Fatty Acids 54, 45-51. http://dx.doi.org/10.1016/S0952-3278 (96)90080-0.
    8. D'Amour FE & Smith DL (1941) A method for determining loss of pain sensation. Journal of Pharmacology and Experimental Therapeutics 72, 74-79.
    9. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A & Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405, 183-187. http://dx.doi.org/10.1038/35012076.
    10. Dhaka A, Viswanath V & Patapoutian A (2006) TRP ion channels and temperature sensation. Annual Review of Neuroscience 29, 135-161. http://dx.doi.org/10.1146/annurev.neuro.29.051605.112958.
    11. Hudson LJ, Bevan S, Wotherspoon G, Gentry C, Fox A & Winter J (2001) VR1 protein expression increases in undamaged DRG neurons after partial nerve injury. Europian Journal of Neuroscience 13: 2105-2114. http://dx.doi.org/10.1046/j.0953-816x.2001.01591.x.
    12. Islam MS (2011) Transient Receptor Potential Channels. Advance in Experimental Medicine and Biology 30, 700.
    13. LaMotte RH, Lundberg LE & Torebjork HE (1992) Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiology-Paris 448, 749-764.
    14. LaMotte RH, Shain CN, Simone DA & Tsai EF (1991) Neurogenic hyperalgesia:psychophysical studies of underlying mechanisms. Journal of Neurophysiology 66, 190-211.
    15. Lawson JJ, McIlwrath SL & Woodbury CJ (2008) TRPV1 unlike TRPV2 is restricted to a subset of mechanically insensitive cutaneous nociceptors responding to heat. Journal of Pain 9, 298-308. http://dx.doi.org/10.1016/j.jpain.2007.12.001.
    16. McNamara FN, Randall A & Gunthorpe MJ (2005) Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1). British Journal of Pharmacoly 144,781-790. http://dx.doi.org/10.1038/sj.bjp.0706040.
    17. Pabbidi RM, Cao DS, Parihar A, Pauza ME & Premkumar LS (2008) direct role of streptozotocin in inducing thermal hyperalgesia by enhanced expression of transient receptor potential vanilloid 1 in sensory neurons. Molecular Pharmacology 73, 995-1004. http://dx.doi.org/10.1124/mol.107.041707.
    18. Patacchini R, Maggi CA & Meli A (1990) Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents. Naunyn Schmiedebergs Arch Pharmacol. 342, 72-77. http://dx.doi.org/10.1007/BF00178975.
    19. Pingle SC, Matta JA & Ahern GP (2007) Capsaicin receptor: TRPV1 a promiscuous TRP channel. Handbook of Experimenal Pharmacology 179, 155-171. http://dx.doi.org/10.1007/978-3-540-34891-7_9.
    20. Prempeh AB & Mensah AJ (2008) Analgesic activity of crude aqueous extract of the root bark of Zanthoxylum Xanthoxyloides. Ghana Medical Journal 42, 79-84.
    21. Rashid MH, Inoue M, Bakoshi S & Ueda H (2003a) Increased expression of vanilloid receptor 1 on myelinated primary afferent neurons contributes to the antihyperalgesic effect of capsaicin cream in diabetic neuropathic pain in mice. Journal of Pharmacology and Experimental Therapeutics 306, 709-717. http://dx.doi.org/10.1124/jpet.103.050948.
    22. Rashid MH, Inoue M, Kondo S, Kawashima T, Bakoshi S & Ueda H. (2003b) Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin cream in neuropathic pain. Journal of Pharmacology and Experimental Therapeutics 304, 940–948. http://dx.doi.org/10.1124/jpet.102.046250.
    23. Simon B, Xue JL, Chun K & Michael WS (2010) Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier. Molecular Pain 6, 74. http://dx.doi.org/10.1186/1744-8069-6-74.
    24. Simone DA & Ochoa J (1991) early and late effects of prolonged topical capsaicin on cutaneous sensibility and neurogenic vasodilatation in humans. Pain 47, 285-294. http://dx.doi.org/10.1016/0304-3959 (91)90217-L.
    25. Simone DA, Baumann TK & LaMotte RH (1989) Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin. Pain 38, 99-107. http://dx.doi.org/10.1016/0304-3959 (89)90079-1.
    26. 26. Spruce MC, Potter J & Coppini DV (2003) the pathogenesis and management of painful diabetic neuropathy: a review. Diabetic Medicine 20, 88-98. http://dx.doi.org/10.1046/j.1464-5491.2003.00852.x.
    27. Szallasi A & Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacological Reviews 51, 159-212.
    28. Szolcsanyi J (1983) Tetrodotoxin-resistant non-cholinergic neurogenic contraction evoked by capsaicinoids and piperine on the guinea-pig trachea. Neuroscience Letter 42, 83-88. http://dx.doi.org/10.1016/0304-3940 (83)90426-3.
    29. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21, 531-543. http://dx.doi.org/10.1016/S0896-6273 (00)80564-4.
    30. Trinder P (1996) Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Annals of Clinical Biochemistry 6, 24. http://dx.doi.org/10.1177/000456326900600108.
    31. Venkatachalam K & Montell C (2007) TRP channels. Annual Review of Biochemistry 76, 387-417. http://dx.doi.org/10.1146/annurev.biochem.75.103004.142819.
    32. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V & Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430, 748-754. http://dx.doi.org/10.1038/nature02732.

  • Downloads

  • How to Cite

    Gohil, P., Shah, G., & Patel, C. (2014). Role of trpv1 (transient receptor potential v1 channel) in piperine induced hyperalgesia: a preliminary study. International Journal of Pharmacology and Toxicology, 2(2), 95-100. https://doi.org/10.14419/ijpt.v2i2.3269