De la O-Arciniega M, Godínez-Chaparro B, Guevara-López U, Cortés-Arroyo AR, López-Muñoz FJ

Language: Spanish
References: 51
Page: 363-369
PDF size: 87.03 Kb.

ABSTRACT

Background: Neuropathic pain is associated with disease or injury to the peripheral or central nervous system, which is considered particularly difficult to treat due to its diverse etiology and underlying physiopathological mechanisms. Recent experimental and clinical data support the potential of pharmacotherapy using a combination of drugs for neuropathic pain.
Methods: In order to assess a possible synergistic anti-hyperalgesic interaction, the anti-hyperalgesic effects of morphine and gabapentin, single-dose administered either separately or in combination, were determined using the von Frey test in a rat model of neuropathic pain (Bennett model).
Results: Time course analysis showed that morphine (3.2 mg/kg SC) and gabapentin (17.8 mg/kg SC) individually reached their maximum effect at 60 min after treatment, producing an anti-hyperalgesic effect of 51.7 ± 10.5 % and 55.0 ± 11.7 %, respectively, whereas the combination morphine + gabapentin (3.2 + 17.8 mg/kg SC) produced an almost total anti-hyperalgesic effect at 30 min (96.7 ± 2.1 %) and at 60 min showed 100 % anti-hyperalgesia. This anti-hyperalgesic effect remained during 180 min of observation. Analysis of global effects as area under the curve of time course showed that the nature of the anti-hyperalgesic interaction of the analyzed dose had an additive effect. There was no significant difference observed in the theoretical sum of anti-hyperalgesic effect produced by each drug alone (225.4 ± 29.1 area units, au) compared with the corresponding effects produced by the combination of drugs (263.33 ± 3.3 au).
Conclusions: These findings are useful in determining the type of interaction that these drugs produce using this combination ratio in neuropathic pain.

REFERENCES

1. Hasson PT, Lacerenza M, Marchettini P. Aspects of clinical and experimental neuropathic pain: the clinical perspective. In: Hasson PT, Fields HL, Hill RG, Marchettini P, eds. Neuropathic Pain: Pathophysiology and Treatment. Progress in Pain Research and Management, Vol. 21. Seattle: IASP Press;2001. pp 1-18.

2. 2. Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003;102:1-8.

3. 3. Guevara-López U, Covarrubias-Gómez A, Hernández-Jiménez S, Palapa-García R, Acosta-Alanís FJ, Aragón G. Tendencias de diagnóstico y tratamiento del dolor neuropático en México. Rev Mex Anest 2006;29:9-14.

4. 4. Jensen TS, Gottrup H, Sindrup SH, Bach FW. The clinical picture of neuropathic pain. Eur J Pharmacol 2001;429:1-11.

5. 5. Vinik AI, Mehrabyan A. Diabetic neuropathies. Med Clin North Am 2004;88:947-999.

6. 6. Grond S, Radbruch L, Meuser T, Sabatowski R, Loick G, Lehmann KA. Assessment and treatment of neuropathic cancer pain following WHO guidelines. Pain 1999;79:15-20.

7. 7. Besson M, Brooka P, Chizh BA, Pickering AE. Tactile allodynia in patients with postherpetic neuralgia: lack of change in skin blood flow upon dynamic stimulation. Pain 2005;117:154-156.

8. 8. Brew BJ, Tomlinson SE. HIV neuropathy: time for new therapies. Drug Discov Today: Disease Models 2004;1:171-176.

9. 9. Backonja M. Defining neuropathic pain. Anesth Analg 2003;97:785-790.

10. 10. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004;140:441-451.

11. 11. Bridges D, Thompson SWN, Rice ASC. Mechanism of neuropathic pain. Br J Anaesth 2001;87:12-26.

12. 12. Ueda H, Rashid H. Molecular mechanism of neuropathic pain. Drug News Perspect 2003;16:605-613.

13. 13. Woolf CJ. Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci 2004;74:2605-2610.

14. 14. Ueda H. Molecular mechanisms of neuropathic pain¾phenotypic switch and initiation mechanisms. Pharmacol Ther 2006;109:57-77.

15. 15. Guevara-López U, Covarrubias-Gómez A, García-Ramos G, Hernández-Jiménez S. Parámetros de práctica para el manejo del dolor neuropático. Rev Invest Clin 2006;58:126-138.

16. 16. Gilron I, Watson P, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ 2006;175:265-275.

17. 17. Micó JA, Ardid D, Berrocoso E, Eschalier A. Antidepressants and pain. Trends Pharmacol Sci 2006;27:348-354.

18. 18. La Roche SM, Helmers SL. The new antiepileptic drugs. Clinical Applications. JAMA 2004;291:615-620.

19. 19. Eisenberg E, McNicol ED, Carr DB. Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin. JAMA 2005;293:3043-3052.

20. 20. Eisenberg E, McNicol ED, Carr DB. Efficacy of µ-opioid agonists in the treatment of evoked neuropathic pain: systematic review of randomized controlled trials. Eur J Pain 2006;10:667-676.

21. 21. Dworkin R, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain. Diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60:1524-1534.

22. 22. Gilron I, Max MB. Combination pharmacotherapy for neuropathic pain: current evidence and future directions. Expert Rev Neurother 2005;5:823-830.

23. 23. López-Muñoz FJ. Surface synergistic interaction between dipyrone and morphine in PIFIR model. Drug Des Rev 1994;33:26-32.

24. 24. Dowdall T, Robinson I, Meert FT. Comparison of five different rat models of peripheral nerve injury. Pharmacol Biochem Behav 2005;80:93-108.

25. 25. Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol 2001;429:23-37.

26. 26. De Vry J, Kuhl E, Franken-Kunkel P, Eckel G. Pharmacological characterization of the chronic constriction injury model of neuropathic pain. Eur J Pharmacol 2004;491:137-148.

27. 27. Hama AT, Borsook D. Behavioral and pharmacological characterization of a distal peripheral nerve injury in the rat. Pharmacol Biochem Behav 2005;81:170-181.

28. 28. Rose MA, Kam PCA. Gabapentin: pharmacology and use in pain management. Anaesthesia 2002;57:451-462.

29. 29. Gilron I, Bailey JM, Tu D, Holden R, Weaver DF, Houlden RF. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med 2005;352:1324-1334.

30. 30. Zimmermann M. Ethical guidelines for investigation of experimental pain in conscious animals. Pain 1983;16:109-110.

31. 31. Bennett G, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107.

32. 32. Xiao W, Boroujerdi A, Bennett GJ, Luo ZD. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit. Neuroscience 2007;144:714-720.

33. 33. Rowland M, Tozer NT. Clinical pharmacokinetics: concepts and applications. Philadelphia: Lea and Febiger;1989.

34. 34. Rang HP, Dale MM, Ritter JM, Moore PK. Farmacología. 5th ed. Madrid: Elsevier;2004.

35. 35. McNamara JO. Pharmacotherapy of the epilepsies. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill;2006. pp. 501-525.

36. 36. Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN. The novel anticonvulsant drug, gabapentin (neurontin), binds to the á2ä subunit of a calcium channel. J Biol Chem 1996;271:5768-5776.

37. 37. Smiley MM, Lu Y, Vera-Portocarrero LP, Zidan A, Westlund KN. Intrathecal gabapentin enhances the analgesic effects of a subtherapeutic dose of morphine in a rat experimental pancreatitis model. Anesthesiology 2004;101:759-765.

38. 38. Lynch III JM, Wade CL, Zhong CM, Mikusa JP, Honore P. Attenuation of mechanical allodynia by clinically utilized drugs in a rat chemotherapy-induced neuropathic pain model. Pain 2004;110:56-63.

39. 39. Hunter JC, Gogas KR, Hedley LR. The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 1997;324:153-160.

40. 40. Takasaki I, Andoh T, Nojima H. Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection. J Pharmacol Exp Ther 2001;296:270-275.

41. 41. Przewlocki R, Przewlocka B. Opioids in chronic pain. Eur J Pharmacol 2001;429:79-91.

42. 42. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004;122:372-380.

43. 43. Gutstein HB, Akil H. Opioid analgesics. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill;2006. pp. 547-590.

44. 44. Tallarida RJ. Statistical analysis of drug combinations for synergism. Pain 1992;49:93-97.

45. 45. Shimoyama M, Shimoyama N, Inturrisi CE, Elliott KJ. Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test. Pain 1997;72:375-382.

46. 46. Gilron I, Biederman J, Jhamandas K, Hong M. Gabapentin blocks and reverses antinociceptive morphine tolerance in the rat paw-pressure and tail-flick tests. Anesthesiology 2003;98:1288-1292.

47. 47. Hansen C, Gilron I, Hong M. The effects of intrathecal gabapentin on spinal morphine tolerance in the rat tail-flick and paw pressure tests. Anesth Analg 2004;99:1180-1184.

48. 48. Meimandi MS, Sepehri GR, Mobasher M, Narges A. Gabapentin increases analgesic effect of chronic use of morphine while decreasing withdrawal signs. Int J Pharm 2005;1:161-166.

49. 49. Matthews EA, Dickenson AH. A combination of gabapentin and morphine mediates enhanced inhibitory effects on dorsal horn neuronal responses in a rat model of neuropathy. Anesthesiology 2002;96:633-640.

50. 50. Dierking G, Duedahl TH, Rasmussen ML, Fomsgaard JS, Møiniche S, Rømsing J, Dahl JB. Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial. Acta Anaesthesiol Scand 2004;48:322-327.

51. 51. Radhakrishnan M, Bithal P, Chaturvedi A. Effect of preemptive gabapentin on postoperative pain relief and morphine consumption following lumbar laminectomy and discectomy. J Neurosurg Anesthesiol 2005;17:125-128.