Drug combinations in diabetic neuropathic pain: an experimental validation
-
Chakra Dhar Tripathi
,
Ashish K. Mehta
Abstract
Background:
Diabetic neuropathy is the most common complication of diabetes mellitus, and the different drug combinations available do not provide effective pain relief. The present study was performed to observe the effect of amitripyline, duloxetine, sitagliptin, and pregabalin, and their combinations on streptozotocin (STZ)-induced diabetic neuropathy.
Methods:
Diabetic neuropathy was induced by STZ, and the tail-flick test was used to assess thermal hyperalgesia before and after (at 30, 60, and 120 min) drug administration. One week after STZ administration, the blood glucose level was observed to be in the diabetic range.
Results:
Administration of all the drugs except sitagliptin increased the tail-flick latency significantly as compared to control. Further, the drugs amitriptyline, duloxetine, and pregabalin showed significant pain-relieving effect, when either two of them were administered in combination, although the different combinations had varied degree of pain relief. However, sitagliptin was observed to have no effect when administered alone or in combination with the other three drugs.
Conclusions:
Therefore, the study provides new insights concerning combined therapy of pain, which further needs clinical exploration.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 2005;28:956–62.10.2337/diacare.28.4.956Suche in Google Scholar PubMed
2. Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med 2004;21:976–82.10.1111/j.1464-5491.2004.01271.xSuche in Google Scholar PubMed
3. Bhadada SK, Sahay RK, Jyostna VP, Agrawal JK. Diabetic neuropathy current concepts. J Indian Acad Clin Med 2001;2:305–31.Suche in Google Scholar
4. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, et al. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011;76:1758–65.10.1016/j.pmrj.2011.03.008Suche in Google Scholar PubMed
5. Schreiber AK, Nones CF, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: physiopathology and treatment. World J Diabetes 2015;6:432–44.10.4239/wjd.v6.i3.432Suche in Google Scholar PubMed PubMed Central
6. Jones CK, Peters SC, Shannon HE. Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther 2005;312:726–32.10.1124/jpet.104.075960Suche in Google Scholar PubMed
7. Kuhad A, Bishnoi M, Chopra K. Anti-nociceptive effect of duloxetine in mouse model of diabetic neuropathic pain. Indian J Exp Biol 2009;47:193–7.Suche in Google Scholar
8. Vranken JH, Hollmann MW, van der Vegt MH, Kruis MR, Heesen M, Vos K, et al. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial. Pain 2011;152:267–73.10.1016/j.pain.2010.09.005Suche in Google Scholar PubMed
9. Li CY, Song YH, Higuera ES, Luo ZD. Spinal dorsal horn calcium channel α2δ-1 subunit upregulation contributes to peripheral nerve injury induced tactile allodynia. J Neurosci 2004;24:8494–9.10.1523/JNEUROSCI.2982-04.2004Suche in Google Scholar PubMed PubMed Central
10. Yusaf SP, Goodman J, Gonzalez IM, Bramwell S, Pinnock RD, Dixon AK, et al. Streptozocin-induced neuropathy is associated with altered expression of voltage-gated calcium channel subunit mRNAs in rat dorsal root ganglion neurones. Biochem Biophys Res Commun 2001;289:402–6.10.1006/bbrc.2001.5943Suche in Google Scholar PubMed
11. Smith T, Nicholson RA. Review of duloxetine in the management of diabetic peripheral neuropathic pain. Vasc Health Risk Manag 2007;3:833–44.Suche in Google Scholar
12. Lackovic Z, Salkovic M, Kuci Z, Relja M. Effect of long-lasting diabetes mellitus on rat and human brain monoamines. J Neurochem 1990;54:143–7.10.1111/j.1471-4159.1990.tb13294.xSuche in Google Scholar PubMed
13. Petrisic MS, Augood SJ, Bicknell RJ. Monoamine transporter gene expression in the central nervous system in diabetes mellitus. J Neurochem 1997;68:2435–41.10.1046/j.1471-4159.1997.68062435.xSuche in Google Scholar PubMed
14. Sawynok J, Reid AR, Esser MJ. Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine. Pain 1999;80:45–55.10.1016/S0304-3959(98)00195-XSuche in Google Scholar
15. McIntosh CH, Demuth HU, Pospisilik JA, Pederson R. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents. Regul Pept 2005;128:159–65.10.1016/j.regpep.2004.06.001Suche in Google Scholar
16. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132:237–51.10.1016/j.pain.2007.08.033Suche in Google Scholar
17. Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010;85:S3–14.10.4065/mcp.2009.0649Suche in Google Scholar
18. Chong MS, Hester J. Diabetic painful neuropathy: current and future treatment options. Drugs 2007;67:569–85.10.2165/00003495-200767040-00006Suche in Google Scholar
19. Courteix C, Eschalier A, Lavarenne J. Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain 1993;53:81–8.10.1016/0304-3959(93)90059-XSuche in Google Scholar
20. Sheikh AS, Somani RS. Animal models and biomarkers of neuropathy in diabetic rodents. Indian J Pharmacol 2010;42:129–34.10.4103/0253-7613.66833Suche in Google Scholar
21. Tomić MA, Vucković SM, Stepanović-Petrović RM, Micov AM, Ugresić ND, Prostran MS, et al. Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice. Eur J Pharmacol 2010;628:75–82.10.1016/j.ejphar.2009.11.016Suche in Google Scholar
22. D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther 1941;72:74–9.Suche in Google Scholar
23. Rakieten N, Rakieten ML, Nadkarni MR. Studies on the diabetogenic action of streptozotocin (NSC-37917). Cancer Chemother Rep 1963;29:91–8.Suche in Google Scholar
24. Guo H, Yang Y, Geng Z, Zhu L, Yuan S, Zhao Y, et al. The change of insulin-like growth factor-1 in diabetic patients with neuropathy. Chin Med J 1999;112:76–9.Suche in Google Scholar
25. Craner MJ, Klein JP, Black JA, Waxman SG. Preferential expression of IGF-1 in small DRG neurons and down-regulation following injury. Neuroreport 2002;13:1649–52.10.1097/00001756-200209160-00016Suche in Google Scholar
26. Calcutt NA, Jorge MC, Yaksh TL, Chaplan SR. Tactile allodynia and formalin hyperalgesia in streptozotocin-diabetic rats: effects of insulin, aldose reductase inhibition and lidocaine. Pain 1996;68:293–9.10.1016/S0304-3959(96)03201-0Suche in Google Scholar
27. Bujalska-Zadrożny M, de Cordé A, Pawlik K. Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy. Pharmacol Rep 2015;67:209–16.10.1016/j.pharep.2014.08.023Suche in Google Scholar
28. Said G. Diabetic neuropathy: a review. Nat Clin Pract Neurol 2007;3:331–40.10.1038/ncpneuro0504Suche in Google Scholar
29. Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev 2001;53:597–652.Suche in Google Scholar
30. Calcutt NA. Potential mechanisms of neuropathic pain in diabetes. Int Rev Neurobiol 2002;50:205–28.10.1016/S0074-7742(02)50078-7Suche in Google Scholar
31. Sullivan KA, Lentz SI, Roberts Jr JL, Feldman EL. Criteria for creating and assessing mouse models of diabetic neuropathy. Curr Drug Targets 2008;9:3–13.10.2174/138945008783431763Suche in Google Scholar
32. Kuraishi Y, Takasaki I, Nojima H, Shiraki K, Takahata H. Effects of the suppression of acute herpetic pain by gabapentin and amitriptyline on the incidence of delayed postherpetic pain in mice. Life Sci 2004;74:2619–26.10.1016/j.lfs.2004.01.005Suche in Google Scholar
33. Courteix C, Bardin M, Chantelauze C, Lavarenne J, Eschalier A. Study of the sensitivity of the diabetes-induced pain model in rats to a range of analgesics. Pain 1994;57:153–60.10.1016/0304-3959(94)90218-6Suche in Google Scholar
34. Max MB, Culnane M, Schafer SC, Gracely RH, Walther DJ, Smoller B, et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987;37:589–96.10.1212/WNL.37.4.589Suche in Google Scholar
35. Engleman EA, Perry KW, Mayle DA, Wong DT. Simultaneous increases of extracellular monoamines in microdialysates from hypothalamus of conscious rats by duloxetine, a dual serotonin and norepinephrine uptake inhibitor. Neuropsychopharmacology 1995;12:287–95.10.1016/0893-133X(94)00093-FSuche in Google Scholar
36. Koch S, Hemrick-Luecke SK, Thompson LK, Evans DC, Threlkeld PG, Nelson DL, et al. Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. Neuropharmacology 2003;45:935–44.10.1016/S0028-3908(03)00268-5Suche in Google Scholar
37. Iyengar S, Webster AA, Hemrick-Luecke SK, Xu JY, Simmons RM. Efficacy of duloxetine, a potent and balanced serotoninnorepinephrine reuptake inhibitor in persistent pain models in rats. J Pharmacol Exp Ther 2004;311:576–84.10.1124/jpet.104.070656Suche in Google Scholar PubMed
38. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology 2004;63:2104–10.10.1212/01.WNL.0000145767.36287.A1Suche in Google Scholar
39. McClelland D, Evans RM, Barkworth L, Martin DJ, Scott RH. A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats. BMC Pharmacol 2004; 4:14.10.1186/1471-2210-4-14Suche in Google Scholar
40. Eckstein-Ludwig U, Fei J, Schwarz W. Inhibition of uptake, steady-state currents, and transient charge movements generated by the neuronal GABA transporter by various anticonvulsant drugs. Br J Pharmacol 1999;128: 92–102.10.1038/sj.bjp.0702794Suche in Google Scholar
41. Ryu JH, Lee PB, Kim JH, Do SH, Kim CS. Effects of pregabalin on the activity of glutamate transporter type 3. Br J Anaesth 2012;109:234–9.10.1093/bja/aes120Suche in Google Scholar
42. Sharma AK, Sharma A, Kumari R, Kishore K, Sharma D, Srinivasan BP, et al. Sitagliptin, sitagliptin and metformin, or sitagliptin and amitriptyline attenuate streptozotocin-nicotinamide induced diabetic neuropathy in rats. J Biomed Res 2012;26:200–10.10.7555/JBR.26.20110054Suche in Google Scholar
43. Zhou JY, Zhou SW. Protection of trigonelline on experimental diabetic peripheral neuropathy. Evid Based Complement Alternat Med 2012;2012:164219.10.1155/2012/164219Suche in Google Scholar
44. Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005;352:1324–34.10.1056/NEJMoa042580Suche in Google Scholar
45. Gilron I, Bailey JM, Tu D, Holden RR, Jackson AC, Houlden RL. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet 2009;374:1252–61.10.1016/S0140-6736(09)61081-3Suche in Google Scholar
46. Gatti A, Sabato AF, Occhioni R, Colini Baldeschi G, Reale C. Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study. Eur Neurol 2009;61:129–37.10.1159/000186502Suche in Google Scholar PubMed
©2016 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Behavior and Neuroprotection
- Analgesic properties of aqueous leaf extract of Haematostaphis barteri: involvement of ATP-sensitive potassium channels, adrenergic, opioidergic, muscarinic, adenosinergic and serotoninergic pathways
- Correlative study of peripheral ATP1A1 gene expression level to anxiety severity score on major depressive disorder patients
- Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice
- Reproduction
- Tobacco smoke exposure induces irreversible alteration of testicular function in prepubertal rats
- Oxidative Stress
- α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice
- Effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 osteoblast-like cells
- Metabolism
- Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome
- Exercise increases the level of plasma orexin A in humans
- Inflammation
- Drug combinations in diabetic neuropathic pain: an experimental validation
- Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy
- Hematology
- Phenotypic homogeneity with minor deviance in osmotic fragility of Sahel goat erythrocytes in non-ionic sucrose media during various physiologic states
- Protection against arsenic-induced hematological and hepatic anomalies by supplementation of vitamin C and vitamin E in adult male rats
- One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity
- Phytotherapy
- Antithrombotic and cytotoxic activities of four Bangladeshi plants and PASS prediction of their isolated compounds
Artikel in diesem Heft
- Frontmatter
- Behavior and Neuroprotection
- Analgesic properties of aqueous leaf extract of Haematostaphis barteri: involvement of ATP-sensitive potassium channels, adrenergic, opioidergic, muscarinic, adenosinergic and serotoninergic pathways
- Correlative study of peripheral ATP1A1 gene expression level to anxiety severity score on major depressive disorder patients
- Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice
- Reproduction
- Tobacco smoke exposure induces irreversible alteration of testicular function in prepubertal rats
- Oxidative Stress
- α-Lipoic acid attenuates transplacental nicotine-induced germ cell and oxidative DNA damage in adult mice
- Effects of nicotine in the presence and absence of vitamin E on morphology, viability and osteogenic gene expression in MG-63 osteoblast-like cells
- Metabolism
- Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome
- Exercise increases the level of plasma orexin A in humans
- Inflammation
- Drug combinations in diabetic neuropathic pain: an experimental validation
- Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy
- Hematology
- Phenotypic homogeneity with minor deviance in osmotic fragility of Sahel goat erythrocytes in non-ionic sucrose media during various physiologic states
- Protection against arsenic-induced hematological and hepatic anomalies by supplementation of vitamin C and vitamin E in adult male rats
- One more health benefit of blood donation: reduces acute-phase reactants, oxidants and increases antioxidant capacity
- Phytotherapy
- Antithrombotic and cytotoxic activities of four Bangladeshi plants and PASS prediction of their isolated compounds
