Srishti Chaudhary, Pankaj Kumar Prashar, Anamika Gautam, Ankita Sood, Sachin Kumar Singh, Monica Gulati, Narendra Kumar Pandey, Bimlesh Kumar
bimlesh1Pharm@gmail.com , firstname.lastname@example.org
Srishti Chaudhary, Pankaj Kumar Prashar, Anamika Gautam, Ankita Sood, Sachin Kumar Singh, Monica Gulati, Narendra Kumar Pandey, Bimlesh Kumar*
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
Volume - 14,
Issue - 5,
Year - 2021
Injury to the nerves causes alteration in normal neurobiological sequences lead to disease of somatosensory nervous system called as neuropathic pain (NP). It affects both central as well as peripheral nervous system. It is a chronic painful condition occurs due to various diseases like HIV, diabetes, lesions, infection, trauma, and metabolic insults. NP affects 7-10% of global population, hence subsequently is a major concern. Pharmacotherapy for NP remains a major clinical challenge due to its complex pathophysiology. Current treatments like Analgesics, anticonvulsants, non-steroidal anti-inflammatory drugs, tri-cyclic antidepressants, sodium channel blocker and opioid agonist administrated individually to patients of NP are providing only meager and partial relief. Furthermore, these drugs have limited efficacy as well as adverse effects. Hence instead of monotherapy, pathophysiology of NP suggests that administering multiple drugs (polypharmacy) show quick and sufficient effect in the treatment of NP. Recent updates indicate that combination of Morphine and gabapentin, Pregabalin and duloxetine, Gabapentin and nortriptyline, Amitriptyline and ketamine (topical), Doxepin and capsaicin (topical), Glyceryl trinitrate (topical) and valproate are also a good choice for the treatment of NP. Several clinical trials also established that combination pharmacotherapy showed greater efficacy than monotherapy in treating NP. Physicians, scientists working in the area of NP are not only looking for its treatment but also in resolving the issues of co-morbidities associated with it. Hence the present review focuses on rationalized approach of combination therapy for the treatment of various aspects of NP.
Cite this article:
Srishti Chaudhary, Pankaj Kumar Prashar, Anamika Gautam, Ankita Sood, Sachin Kumar Singh, Monica Gulati, Narendra Kumar Pandey, Bimlesh Kumar. Rationalized Approach for The Treatment of Neuropathic Pain. Research Journal of Pharmacy and Technology. 2021; 14(5):2887-5. doi: 10.52711/0974-360X.2021.00507
Srishti Chaudhary, Pankaj Kumar Prashar, Anamika Gautam, Ankita Sood, Sachin Kumar Singh, Monica Gulati, Narendra Kumar Pandey, Bimlesh Kumar. Rationalized Approach for The Treatment of Neuropathic Pain. Research Journal of Pharmacy and Technology. 2021; 14(5):2887-5. doi: 10.52711/0974-360X.2021.00507 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-5-91
1. Colloca, L., et al., Neuropathic pain. Nature Reviews Disease Primers, 2017. 3: p. 17002.
2. VanDenKerkhof, E.G., et al., An epidemiological study of neuropathic pain symptoms in Canadian adults. Pain Research and Management, 2016. 2016.
3. Kaur, M., et al., Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats. European Journal of Pharmacology, 2017. 805: p. 58-66.
4. Khangura, R.K., et al., Neuropathic pain attenuating effects of perampanel in an experimental model of chronic constriction injury in rats. Biomedicine & Pharmacotherapy, 2017. 94: p. 557-563.
5. Kumar, A., D. Pahwa, and P. Rinwa, Management of neuropathic pain: challenges and opportunities. Int J Res Dev Pharm L Sci, 2013. 3: p. 734-740.
6. Argov, Z. and F.L. Mastaglia, Drug-induced peripheral neuropathies. Br Med J, 1979. 1(6164): p. 663-666.
7. Vilholm, O.J., et al., Drug‐induced peripheral neuropathy. Basic & Clinical Pharmacology & Toxicology, 2014. 115(2): p. 185-192.
8. Cruccu, G. and A. Truini, A review of neuropathic pain: from guidelines to clinical practice. Pain and Therapy, 2017. 6(1): p. 35-42.
9. Attal, N., et al., The specific disease burden of neuropathic pain: results of a French nationwide survey. Pain, 2011. 152(12): p. 2836-2843.
10. Bouhassira, D., et al., Development and validation of the neuropathic pain symptom inventory. Pain, 2004. 108(3): p. 248-257.
11. Bouhassira, D., et al., Prevalence of chronic pain with neuropathic characteristics in the general population. Pain, 2008. 136(3): p. 380-387.
12. Freynhagen, R., et al., Screening of neuropathic pain components in patients with chronic back pain associated with nerve root compression: a prospective observational pilot study (MIPORT). Current Medical Research and Opinion, 2006. 22(3): p. 529-537.
13. Raafat, K., et al., Neuropathic Pain: Literature Review and Recommendations of Potential Phytotherapies. Pharmacognosy Journal, 2017. 9(4).
14. Hsieh, H.-L. and C.-M. Yang, Role of redox signaling in neuroinflammation and neurodegenerative diseases. BioMed Research International, 2013. 2013.
15. Jensen, T.S. and N.B. Finnerup, Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. The Lancet Neurology, 2014. 13(9): p. 924-935.
16. Yoon, C., et al., Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain, 1994. 59(3): p. 369-376.
17. Campbell, J.N., et al., Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain, 1988. 32(1): p. 89-94.
18. Wang, Y., et al., Effect of KN-93 on thermal hyperalgesia and expression of pCREB in spinal dorsal horn neurons in a rat model of neuropathic pain. The Journal of Clinical Anesthesiology, 2009. 25(2): p. 151-153.
19. Baron, R., Mechanisms of disease: neuropathic pain—a clinical perspective. Nature clinical practice Neurology, 2006. 2(2): p. 95-106.
20. Bridges, D., S. Thompson, and A. Rice, Mechanisms of neuropathic pain. British Journal of Anaesthesia, 2001. 87(1): p. 12-26.
21. Zhuo, M., G. Wu, and L.-J. Wu, Neuronal and microglial mechanisms of neuropathic pain. Molecular Brain, 2011. 4(1): p. 31.
22. Baron, R., et al., Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain, 2017. 158(2): p. 261.
23. Campbell, J.N. and R.A. Meyer, Mechanisms of neuropathic pain. Neuron, 2006. 52(1): p. 77-92.
24. Ueda, H., Molecular mechanisms of neuropathic pain–phenotypic switch and initiation mechanisms. Pharmacology & Therapeutics, 2006. 109(1): p. 57-77.
25. Costigan, M., J. Scholz, and C.J. Woolf, Neuropathic pain: a maladaptive response of the nervous system to damage. Annual Review of Neuroscience, 2009. 32: p. 1-32.
26. Petrenko, A.B., et al., The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review. Anesthesia & Analgesia, 2003. 97(4): p. 1108-1116.
27. Kuner, R., Central mechanisms of pathological pain. Nature Medicine, 2010. 16(11): p. 1258.
28. Calvo, M. and D.L. Bennett, The mechanisms of microgliosis and pain following peripheral nerve injury. Experimental neurology, 2012. 234(2): p. 271-282.
29. Kawasaki, Y., et al., Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1β, interleukin-6, and tumor necrosis factor-α in regulating synaptic and neuronal activity in the superficial spinal cord. Journal of Neuroscience, 2008. 28(20): p. 5189-5194.
30. Lerch, J.K., et al., Stress increases peripheral axon growth and regeneration through glucocorticoid receptor-dependent transcriptional programs. eNeuro, 2017: p. ENEURO. 0246-17.2017.
31. Woolf, C.J., P. Shortland, and R.E. Coggeshall, Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature, 1992. 355(6355): p. 75.
32. Kohama, I., K. Ishikawa, and J.D. Kocsis, Synaptic reorganization in the substantia gelatinosa after peripheral nerve neuroma formation: aberrant innervation of lamina II neurons by Aβ afferents. Journal of Neuroscience, 2000. 20(4): p. 1538-1549.
33. Todd, A.J., Neuronal circuitry for pain processing in the dorsal horn. Nature Reviews Neuroscience, 2010. 11(12): p. 823.
34. Takazawa, T. and A.B. MacDermott, Synaptic pathways and inhibitory gates in the spinal cord dorsal horn. Annals of the New York Academy of Sciences, 2010. 1198(1): p. 153-158.
35. Wolfe, F., et al., The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis & Rheumatology, 1990. 33(2): p. 160-172.
36. Binshtok, A.M., et al., Nociceptors are interleukin-1β sensors. Journal of Neuroscience, 2008. 28(52): p. 14062-14073.
37. Woolf, C.J. and R.J. Mannion, Neuropathic pain: aetiology, symptoms, mechanisms, and management. The lancet, 1999. 353(9168): p. 1959-1964.
38. Xu, B., et al., Translational investigation and treatment of neuropathic pain. Molecular pain, 2012. 8(1): p. 15.
39. Vranken, J.H., Mechanisms and treatment of neuropathic pain. Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Central Nervous System Agents), 2009. 9(1): p. 71-78.
40. Fornasari, D., Pharmacotherapy for Neuropathic Pain: A Review. Pain and therapy, 2017. 6(1): p. 25-33.
41. Finnerup, N.B., S.H. Sindrup, and T.S. Jensen, Management of painful neuropathies, in Handbook of Clinical Neurology. 2013, Elsevier. p. 279-290.
42. Backonja, M. and R.L. Glanzman, Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clinical Therapeutics, 2003. 25(1): p. 81-104.
43. Namaka, M., et al., A treatment algorithm for neuropathic pain. Clinical Therapeutics, 2004. 26(7): p. 951-979.
44. Katsuyama, S., et al., Antinociceptive Effects of the Serotonin and Noradrenaline Reuptake Inhibitors Milnacipran and Duloxetine on Vincristine-Induced Neuropathic Pain Model in Mice. ISRN Pain, 2014. 2014.
45. Bymaster, F.P., et al., Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology, 2001. 25(6): p. 871-880.
46. Muneoka, K., et al., Brain region-specific effects of short-term treatment with duloxetine, venlafaxine, milnacipran and sertraline on monoamine metabolism in rats. Neurochemical Research, 2009. 34(3): p. 542-555.
47. Ye, W., et al., Treatment patterns associated with Duloxetine and Venlafaxine use for Major Depressive Disorder. BMC psychiatry, 2011. 11(1): p. 19.
48. Dupuis, A., et al., Increasing spinal 5-HT2A receptor responsiveness mediates anti-allodynic effect and potentiates fluoxetine efficacy in neuropathic rats. Evidence for GABA release. Pharmacological Research, 2017. 118: p. 93-103.
49. Gilron, I., et al., Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. The Lancet, 2009. 374(9697): p. 1252-1261.
50. Miranda, H.F., et al., Synergism between gabapentin–tramadol in experimental diabetic neuropathic pain. Fundamental & Clinical Pharmacology, 2018.
51. Szczudlik, A., et al., Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the Study of Pain and the Polish Neurological Society–part two. Neurologia I Neurochirurgia Polska, 2014. 48(6): p. 423-435.
52. Le Cudennec, C. and V. Castagné, Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine. European Journal of Pharmacology, 2014. 735: p. 17-25.
53. Arner, S. and B. Meyerson, Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain, 1988. 33(1): p. 11-23.
54. Banafshe, H.R., et al., Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement of opioid system. European Journal of Pharmacology, 2014. 723: p. 202-206.
55. Grenald, S.A., et al., Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists. Neuropharmacology, 2017. 116: p. 59-70.
56. Kazantzis, N.P., et al., Opioid and cannabinoid synergy in a mouse neuropathic pain model. British Journal of Pharmacology, 2016. 173(16): p. 2521-2531.
57. Peterson, C.D., et al., Bivalent ligand that activates mu opioid receptor and antagonizes mGluR5 receptor reduces neuropathic pain in mice. Pain, 2017. 158(12): p. 2431-2441.
58. Farghaly, H., et al., The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model. Pain Physician, 2014. 17(2): p. 187-195.
59. Shinozaki, T., et al., Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats. Journal of Anesthesia, 2015. 29(3): p. 386-395.
60. Alles, S.R. and P.A. Smith, Etiology and pharmacology of neuropathic pain. Pharmacological Reviews, 2018. 70(2): p. 315-347.
61. Schreiber, A.K., et al., Diabetic neuropathic pain: physiopathology and treatment. World Journal of Diabetes, 2015. 6(3): p. 432.
62. Finnerup, N.B., et al., Algorithm for neuropathic pain treatment: an evidence based proposal. Pain, 2005. 118(3): p. 289-305.
63. Davis, M.P., Cancer-Related Neuropathic Pain: Review and Selective Topics. Hematology/Oncology Clinics of North America, 2018.
64. Murnion, B.P., Neuropathic pain: current definition and review of drug treatment. Australian Prescriber, 2018. 41(3): p. 60.
65. Mercadante, S., et al., Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study. Tumori Journal, 2002. 88(3): p. 239-242.
66. McCleane, G.J., A randomised, double blind, placebo controlled crossover study of the cholecystokinin 2 antagonist L-365,260 as an adjunct to strong opioids in chronic human neuropathic pain. Neuroscience Letters, 2003. 338(2): p. 151-154.
67. Lynch, M., A. Clark, and J. Sawynok, A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain. The Clinical Journal of Pain, 2003. 19(5): p. 323-328.
68. Caraceni, A., et al., Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. Journal of Clinical Oncology, 2004. 22(14): p. 2909-2917.
69. Gilron, I., et al., Morphine, gabapentin, or their combination for neuropathic pain. New England Journal of Medicine, 2005. 352(13): p. 1324-1334.
70. Lynch, M.E., et al., Topical 2% Amitriptyline and 1% Ketamine in Neuropathic Pain SyndromesA Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology: The Journal of the American Society of Anesthesiologists, 2005. 103(1): p. 140-146.
71. Khoromi, S., et al., Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain. Pain, 2007. 130(1-2): p. 66-75.
72. Freeman, R., et al., Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy. Current medical Research and Opinion, 2007. 23(1): p. 147-161.
73. Keskinbora, K., A.F. Pekel, and I. Aydinli, Gabapentin and an opioid combination versus opioid alone for the management of neuropathic cancer pain: a randomized open trial. Journal of Pain and Symptom Management, 2007. 34(2): p. 183-189.
74. Hanna, M., C. O'brien, and M.C. Wilson, Prolonged‐release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. European Journal of Pain, 2008. 12(6): p. 804-813.
75. Tonet, C., et al., Avaliação da cetamina oral para dor neuropática. Rev Bras Med, 2008. 65(7).
76. Eichenberger, U., et al., Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds. Anesthesia & Analgesia, 2008. 106(4): p. 1265-1273.
77. Agrawal, R., et al., Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: a prospective double-blind randomized placebo-controlled study. Diabetes Research and Clinical Practice, 2009. 83(3): p. 371-378.
78. Baron, R., et al., 5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study. Current Medical Research and Opinion, 2009. 25(7): p. 1663-1676.
79. Zin, C.S., et al., A randomized, controlled trial of oxycodone versus placebo in patients with postherpetic neuralgia and painful diabetic neuropathy treated with pregabalin. The Journal of Pain, 2010. 11(5): p. 462-471.
80. Amr, Y.M., Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician, 2010. 13(3): p. 245-9.
81. Barton, D.L., et al., A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Supportive Care in Cancer, 2011. 19(6): p. 833-841.
82. Tesfaye, S., et al., Duloxetine and pregabalin: high-dose monotherapy or their combination? The “COMBO-DN study”–a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain. Pain, 2013. 154(12): p. 2616-2625.
83. Harrison, T., et al., Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies. Pain Medicine, 2013. 14(7): p. 1039-1047.
84. Irving, G., et al., Comparative safety and tolerability of duloxetine vs. pregabalin vs. duloxetine plus gabapentin in patients with diabetic peripheral neuropathic pain. International Journal of Clinical Practice, 2014. 68(9): p. 1130-1140.
85. Finnerup, N.B., S.H. Sindrup, and T.S. Jensen, The evidence for pharmacological treatment of neuropathic pain. Pain, 2010. 150(3): p. 573-581.
86. Attal, N., et al., EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European Journal of Neurology, 2010. 17(9): p. 1113-e88.
87. Finnerup, N.B., et al., Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. The Lancet Neurology, 2015. 14(2): p. 162-173.
88. Holbech, J.V., et al., Combination treatment of neuropathic pain: Danish expert recommendations based on a Delphi process. Journal of Pain Research, 2017. 10: p. 1467.
89. Holbech, J.V., et al., Imipramine and pregabalin combination for painful polyneuropathy: a randomized controlled trial. Pain, 2015. 156(5): p. 958-966.
90. Lee, J.H., C.-S. Lee, and U.E.S. Group, A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain. Clinical Therapeutics, 2013. 35(11): p. 1830-1840.
91. Singh, P.M., et al., Analgesic efficacy and safety of medical therapy alone vs combined medical therapy and extraoral glossopharyngeal nerve block in glossopharyngeal neuralgia. Pain Medicine, 2013. 14(1): p. 93-102.
92. Silver, M., et al., Double-blind, placebo-controlled trial of lamotrigine in combination with other medications for neuropathic pain. Journal of Pain and Symptom Management, 2007. 34(4): p. 446-454.