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RESEARCH PAPER
Influence of bee venom on antinociceptive activity of selected analgesic drugs in hot plate test in mice
1
Department of Experimental Pharmacology, Institute of Rural Health, Lublin, Poland
2
Department of Humanities and Social Medicine, Medical University, Lublin, Poland
3
Vincent Pol University in Lublin, Poland
4
Institute of Rural Health, Lublin, Poland
5
Department of Occupational Medicine, Medical University, Lublin, Poland
Corresponding author
KEYWORDS
TOPICS
Prevention of occupational diseases in agriculture, forestry, food industry and wood industryState of the health of rural communities depending on various factors: social factors, accessibility of medical care, etc.
ABSTRACT
Introduction and objective:
The aim of the study was to investigate the effect of bee venom on the activity of two analgesics: ketoprofen (a non-steroidal anti-inflammatory drug) and tramadol (an opioid drug) in the acute thermal pain model (hot-plate test) in mice.
Material and methods:
Linear regression analysis was used to evaluate the dose-response relationship between logarithms of drug doses and their resultant maximum possible anti-nociceptive effects in the mouse hot-plate test. Doses that increased the anti-nociceptive effect by 20% (ED20 values) for bee venom, ketoprofen and tramadol, and their combination were calculated from linear equations. The interaction between bee venom and the selected anaglesics was evaluated using isobolographic analysis.
Results:
The study showed that all compounds produced a definite anti-nociceptive effect, and the experimentally-derived ED20 values for bee venom, ketoprofen and tramadol, when applied indivisually, was 3.64 mg/kg, 79.88 mg/kg and 13.26 mg/kg, respectively. Isobolographic analysis revealed that the combination of bee venom and ketoprofen at a fixed ratio of 1:1 was supra-additive (synergistic). The experimentally-derived ED20 mix was 26.33 mg/kg, which significantly differed from the ED20 add of 41.76 mg/kg (p < 0.5). The experimentally-derived ED20 mix of bee venom and tramadol was 2.90 mg/kg, and differed significantly from the theoretically estimated ED20 add of 8.45 mg/kg (p < 0.5), also indicating a synergistic interaction in the hot-plate test in mice. Moreover, none of the tested combinations indicated any adverse effects in the chimney test and the grip-strength test in mice.
Conclusions:
Overall, the obtained results demonstrated that bee venom significantly increased the anti-nociceptive activity of ketoprofen and tramadol in the hot-plate model of nociceptive pain in mice.
The aim of the study was to investigate the effect of bee venom on the activity of two analgesics: ketoprofen (a non-steroidal anti-inflammatory drug) and tramadol (an opioid drug) in the acute thermal pain model (hot-plate test) in mice.
Material and methods:
Linear regression analysis was used to evaluate the dose-response relationship between logarithms of drug doses and their resultant maximum possible anti-nociceptive effects in the mouse hot-plate test. Doses that increased the anti-nociceptive effect by 20% (ED20 values) for bee venom, ketoprofen and tramadol, and their combination were calculated from linear equations. The interaction between bee venom and the selected anaglesics was evaluated using isobolographic analysis.
Results:
The study showed that all compounds produced a definite anti-nociceptive effect, and the experimentally-derived ED20 values for bee venom, ketoprofen and tramadol, when applied indivisually, was 3.64 mg/kg, 79.88 mg/kg and 13.26 mg/kg, respectively. Isobolographic analysis revealed that the combination of bee venom and ketoprofen at a fixed ratio of 1:1 was supra-additive (synergistic). The experimentally-derived ED20 mix was 26.33 mg/kg, which significantly differed from the ED20 add of 41.76 mg/kg (p < 0.5). The experimentally-derived ED20 mix of bee venom and tramadol was 2.90 mg/kg, and differed significantly from the theoretically estimated ED20 add of 8.45 mg/kg (p < 0.5), also indicating a synergistic interaction in the hot-plate test in mice. Moreover, none of the tested combinations indicated any adverse effects in the chimney test and the grip-strength test in mice.
Conclusions:
Overall, the obtained results demonstrated that bee venom significantly increased the anti-nociceptive activity of ketoprofen and tramadol in the hot-plate model of nociceptive pain in mice.
REFERENCES (63)
1.
Woodcock J. A difficult balance--pain management, drug safety, and the FDA. N Engl J Med. 2009;361(22):2105–2107.
3.
Yekkirala AS, Roberson DP, Bean BP, Woolf CJ. Breaking barriers to novel analgesic drug development. Nat Rev Drug Discov. 2017;16(8):545–564.
4.
Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy. 2013;33(2):195–209.
5.
Han Ch, Cui B. Pharmacological and Pharmacokinetic Studies with Agaricoglycerides, Extracted from Grifolafrondosa, in Animal Models of Pain and Inflammation. Inflammation. 2012;35(4):1269–1275.
6.
Łuszczki JJ, Florek-Łuszczki M. Synergistic interaction of pregabalin with the synthetic cannabinoid WIN 55,212–2 mesylate in the hot-plate test in mice: an isobolographic analysis. Pharmacol Rep. 2012;64(3):723–732.
7.
Goyal S, Goyal S, Goins AE, Alles SRA. Plant-derived natural products targeting ion channels for pain. Neurobiol Pain. 2023;13:100128.
8.
Rengasamy KRR, Mahomoodally MF, Joaheer T, Zhang Y. A Systematic Review of Traditionally Used Herbs and Animal-Derived Products as Potential Analgesics. Curr Neuropharmacol. 2021;19(4):553–588.
9.
Merlo LA, Bastos LF, Godin AM, Rocha LT, Nascimento EB Jr, Paiva AL, Moraes-Santos T, Zumpano AA, Bastos EM, Heneine LG, Coelho MM. Effects induced by Apis mellifera venom and its components in experimental models of nociceptive and inflammatory pain. Toxicon. 2011;57(5):764–71.
10.
Vetter RS, Visscher PK. Bites and stings of medically important venomous arthropods. Int J Dermatol. 1998;37:481–496.
11.
Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 2007;115:246–270.
12.
Ullah A, Aldakheel FM, Anjum SI, Raza G, Khan SA, Tlak Gajger I. Pharmacological properties and therapeutic potential of honey bee venom. Saudi Pharm J. 2023;31(1):96–109.
13.
Sung SH, Lee G. Bee Venom Acupuncture Effects on Pain and Its Mechanisms: An Updated Review. Toxins (Basel). 2021;13(9):608.
14.
Moreno M, Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins. 2015;7:1126–1150.
15.
Kwon YB, Lee JD, Lee HJ, Han HJ, Mar WC, Kang SK, Beitz AJ, Lee JH. Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. Pain. 2001;90:271–280.
16.
Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ, Lee JH. The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats. Life Sci. 2002;71:191–204.
17.
Kang SS, Pak SC, Choi SH. The effect of whole bee venom on arthritis. Am J Chin Med. 2002;30:73–80.
18.
Lee JD, Kim SY, Kim TW, Lee SH, Yang HI, Lee DI, Lee YH. Antiinflammatory effect of bee venom on type II collagen-induced arthritis. Am J Chin Med. 2004;32:361–367.
19.
Lee JD, Park HJ, Chae Y, Lim S. An overview of bee venom acupuncture in the treatment of arthritis. Evid Based Complement Alternat Med. 2005;2:79–84.
20.
Lee JY, Kang SS, Kim JH, Bae CS, Choi SH. Inhibitory effect of whole bee venom in adjuvant-induced arthritis. In Vivo. 2005;19(4):801–805.
21.
Baek YH, Huh JE, Lee JD, Choi DY, Park DS. Antinociceptive effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory pain in the rat model of collagen-induced arthritis: mediation by alpha2-adrenoceptors. Brain Res. 2006;1073–1074:305–310.
22.
Chen CY, Chen WX, Sun X. Comparison of anti-inflammatory, analgesic activities, anaphylactogenicity and acute toxicity between bee venom and its peptides. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1993;13(4):226–227,198. Chinese.
23.
Lee JH, Kwon YB, Han HJ, Mar WC, Lee HJ, Yang IS, Beitz AJ, Kang SK. Bee venom pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced inflammation. J Vet Med Sci. 2001;63(3):251–259.
24.
Kwon YB, Kang MS, Kim HW, Ham TW, Yim YK, Jeong SH, Park DS, Choi DY, Han HJ, Beitz AJ, Lee JH. Antinociceptive effects of bee venom acupuncture (apipuncture) in rodent animal models: a comparative study of acupoint versus non-acupoint stimulation. Acupunct Electrother Res. 2001;26(1–2):59–68.
25.
Kim HW, Kwon YB, Han HJ, Yang IS, Beitz AJ, Lee JH. Antinociceptive mechanisms associated with diluted bee venom acupuncture (apipuncture) in the rat formalin test: involvement of descending adrenergic and serotonergic pathways. Pharmacol Res. 2005;51(2):183–188.
26.
Roh DH, Kim HW, Yoon SY, Kang SY, Kwon YB, Cho KH, Han HJ, Ryu YH, Choi SM, Lee HJ, Beitz AJ, Lee JH. Bee venom injection significantly reduces nociceptive behavior in the mouse formalin test via capsaicin-insensitive afferents. J Pain. 2006;7(7):500–512.
27.
Kwon YB, Kang MS, Han HJ, Beitz AJ, Lee JH. Visceral antinociception produced by bee venom stimulation of the Zhongwan acupuncture point in mice: role of alpha(2) adrenoceptors. Neurosci Lett. 2001;308(2):133–137.
28.
Costa MF, Campos AR, Abdon AP, Vasconcelos RP, Castro CA, Toyama MH, Monteiro HAS, Martins AMC. Study of visceral antinociceptive potential of bee Apis mellifera venom. Afr J Pharm Pharmacol. 2014;8:781–785.
29.
Choi J, Jeon C, Lee JH, Jang JU, Quan FS, Lee K, Kim W, Kim SK. Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α₂-Adrenergic Receptor. Toxins (Basel) 2017;9(11):351.
30.
Roh DH, Kwon YB, Kim HW, Ham TW, Yoon SY, Kang SY, Han HJ, Lee HJ, Beitz AJ, Lee JH. Acupoint stimulation with diluted bee venom (apipuncture) alleviates thermal hyperalgesia in a rodent neuropathic pain model: involvement of spinal alpha 2-adrenoceptors. J Pain. 2004;5(6):297–303.
31.
Kang SY, Roh DH, Choi JW, Ryu Y, Lee JH. Repetitive Treatment with Diluted Bee Venom Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury Model. Toxins (Basel). 2015;7(7):2571–85.
32.
Yoon SY, Yeo JH, Han SD, Bong DJ, Oh B, Roh DH. Diluted bee venom injection reduces ipsilateral mechanical allodynia in oxaliplatin-induced neuropathic mice. Biol Pharm Bull. 2013;36(11):1787–93.
33.
Yeo JH, Yoon SY, Kwon SK, Kim SJ, Lee JH, Beitz AJ, Roh DH. Repetitive Acupuncture Point Treatment with Diluted Bee Venom Relieves Mechanical Allodynia and Restores Intraepidermal Nerve Fiber Loss in Oxaliplatin-Induced Neuropathic Mice. J Pain. 2016;17(3):298–309.
34.
Kim SJ, Yeo JH, Yoon SY, Roh DH. GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model. Integr Med Res. 2023;12(4):100999.
35.
Zegpi C, Gonzalez C, Pinardi G, Miranda HF. The effect of opioid antagonists on synergism between dexketoprofen and tramadol. Pharmacol Res. 2009;60(4):291–295.
36.
Picard P, Bazin JE, Conio N, Ruiz F, Schoeffler P. Ketorolac potentiates morphine in postoperative patient-controlled analgesia. Pain. 1997;73(3):401–406.
37.
Wideman GL, Keffer M, Morris E, Doyle RT Jr, Jiang JG, Beaver WT. Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain. Clin Pharmacol Ther. 1999;65(1):66–76.
38.
Mao J, Gold MS, Backonja MM. Combination drug therapy for chronic pain: a call for more clinical studies. J Pain. 2011;12(2):157–66.
39.
Miranda HF, Puig MM, Prieto JC, Pinardi G. Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain. Pain. 2006;121(1–2):22–28.
40.
Miranda HF, Romero MA, Puig MM. Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice. Fundam Clin Pharmacol. 2012;26(3):373–382.
41.
Łuszczki JJ. Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hot-plate test in mice. Pharmacol Rep. 2010;62(5):942–948.
42.
Schmauss C, Yaksh TL. In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther. 1984;228(1):1–12.
43.
Luszczki JJ, Kołacz A, Wojda E, Czuczwar M, Przesmycki K, Czuczwar SJ. Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: an isobolographic analysis. Pharmacol Rep. 2009;61(3):459–467.
44.
Florek-Luszczki M, Zagaja M, Luszczki JJ. Influence of arachidonyl-2’-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the anticonvulsant and acute side-effect potentials of clobazam, lacosamide, and pregabalin in the maximal electroshock-induced seizure model and chimney test in mice. Fundam Clin Pharmacol. 2015;29(4):382–393.
45.
Zagaja M, Bryda J, Szewczyk A, Szala-Rycaj J, Łuszczki JJ, Walczak M, Kuś K, Andres-Mach M. Xanthotoxin enhances the anticonvulsant potency of levetiracetam and valproate in the 6-Hz corneal stimulation model in mice. Fundam Clin Pharmacol. 2022;36(1):133–142.
46.
Luszczki JJ, Patrzylas P, Zagaja M, Andres-Mach M, Zaluska K, Kondrat-Wrobel MW, Szpringer M, Chmielewski J, Florek-Luszczki M. Effects of arachidonyl-2’-chloroethylamide (ACEA) on the protective action of various antiepileptic drugs in the 6-Hz corneal stimulation model in mice. PLoS One. 2017;12(8):e0183873.
47.
Tallarida RJ. Drug synergism and dose-effect data analysis. Boca Raton, FL: Chapman & Hall/CRC Press; 2000.
48.
Kwon YB, Ham TW, Kim HW, Roh DH, Yoon SY, Han HJ, Yang IS, Kim KW, Beitz AJ, Lee JH. Water soluble fraction (<10 kDa) from bee venom reduces visceral pain behavior through spinal alpha 2-adrenergic activity in mice. Pharmacol Biochem Behav. 2005;80(1):181–187.
49.
Kang SY, Roh DH, Park JH, Lee HJ, Lee JH. Activation of Spinal α2-Adrenoceptors Using Diluted Bee Venom Stimulation Reduces Cold Allodynia in Neuropathic Pain Rats. Evid Based Complement Alternat Med. 2012:784713.
50.
Kim KH, Lee WR, An HJ, Kim JY, Chung H, Han SM, Lee ML, Lee KG, Pak SC, Park KK. Bee venom ameliorates compound 48/80-induced atopic dermatitis-related symptoms. Int J Clin Exp Pathol. 2013;6(12):2896–903.
51.
Silva J, Monge-Fuentes V, Gomes F, Lopes K, dos Anjos L, Campos G, Arenas C, Biolchi A, Gonçalves J, Galante P, Campos L, Mortari M. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools. Toxins (Basel). 2015;7(8):3179–3209.
52.
Kubota T, Komatsu H, Kawamoto H, Yamada T. Studies on the effects of anti-inflammatory action of benzoyl-hydrotropic acid (ketoprofen) and other drugs, with special reference to prostaglandin synthesis. Arch Int Pharmacodyn Ther. 1979;237(1):169–176.
53.
Walker JS. NSAID: an update on their analgesic effects. Clin Exp Pharmacol Physiol. 1995; 22(11): 855–860.
55.
Díaz-Reval MI, Ventura-Martínez R, Hernández-Delgadillo GP, Domínguez-Ramírez AM, López-Muñoz FJ. Effect of caffeine on antinociceptive action of ketoprofen in rats. Arch Med Res. 2001;32(1):13–20.
56.
Medina-López R, Vara-Gama N, Soria-Arteche O, Moreno-Rocha LA, López-Muñoz FJ. Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats. Pharmaceutics. 2018;10(1):20.
57.
Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43:879–923.
58.
Scott LJ, Perry CM. 2000. Tramadol: a review of its use in perioperative pain. Drugs. 60:139–176.
59.
Raffa RB. Pharmacology of oral combination analgesics: rational therapy for pain. J Clin Pharm Ther. 2001;26(4):257–264.
60.
Kim W, Kim MJ, Go D, Min BI, Na HS, Kim SK. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice. Toxins (Basel). 2016;8(2):33.
61.
Yoon SY, Roh DH, Kwon YB, Kim HW, Seo HS, Han HJ, Lee HJ, Beitz AJ, Lee JH. Acupoint stimulation with diluted bee venom (apipuncture) potentiates the analgesic effect of intrathecal clonidine in the rodent formalin test and in a neuropathic pain model. J Pain. 2009;10(3):253–263.
62.
Miranda HF, Pinardi G. Isobolographic analysis of the antinociceptive interactions of clonidine with nonsteroidal anti-inflammatory drugs. Pharmacol Res. 2004;50(3):273–278.
63.
Raffa RB, Pergolizzi JV Jr, Tallarida RJ. The determination and application of fixed-dose analgesic combinations for treating multimodal pain. J Pain. 2010;11(8):701–709.
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