The “gut-brain axis” or “brain-gut axis” communication mechanism has a bidirectional approach because it depends on showing top-down or bottom-up channels to function. It is one of the few systems in the body that combines neuronal routes with humoral pathways, which include cytokines, hormones, and neuropeptides as chemical messages. It was also discovered to be diverse because it contains spinal, vagus, sympathetic, and intestinal nerves. The role of microbes as signaling agents in the gut-brain axis has been proven by the most recent research, which is primarily based on animal models. Probiotics are living bacteria that improve one’s health when ingested in large enough doses. Gut microbes are suspected to play a role in a variety of psychiatric disorders, making them a potential therapeutic target. The stomach and the brain are linked via a two-way communication pathway called the microbiota-gut-brain axis. Current interventional research on probiotics and the gut-brain axis has been evaluated for its findings in the treatment of depression, anxiety, and schizophrenia. Neuropathic pain is brought on by a lesion or injury to the nerve system, which is further demonstrated by a malfunction of the somatosensory system. Such a developed form of pain affects both peripheral and central nervous system neurons. According to research, probiotics can enhance the gut’s dynamic environment and are good for both the gut and the brain. Therefore, the focus of this review is on how probiotics, the microbiota-gut-brain axis, and the gut-brain axis relate to neuropathic pain.

1. Baron R, Binder A, Wasner G. Neuropathic pain: Diagnosis, pathophysiological mechanisms, and treatment. The Lancet Neurology 2010; 9(8): 807–819. doi: 10.1016/S1474-4422(10)70143-5

2. D’Egidio F, Lombardozzi G, Kacem Ben Haj M’Barek HE, et al. The Influence of dietary supplementations on neuropathic pain. Life 2022; 12(8): 1125. doi: 10.3390/life12081125

3. Mäntyselkä P, Kumpusalo E, Ahonen R, et al. Pain as a reason to visit the doctor: A study in Finnish primary health care. Pain 2001; 89(2–3): 175–180. doi: 10.1016/S0304-3959(00)00361-4

4. Haanpää ML, Backonja MM, Bennett MI, et al. Assessment of neuropathic pain in primary care. The American Journal of Medicine 2009; 122(10): S13–S21. doi: 10.1016/j.amjmed.2009.04.006

5. Woolf CJ, Mannion RJ. Neuropathic pain: Aetiology, symptoms, mechanisms, and management. The lancet 1999; 353(9168): 1595–1964. doi: 10.1016/S0140-6736(99)01307-0

6. Dworkin RH, O’connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: Evidence-based recommendations. Pain 2007; 132(3): 237–251. doi: 10.1016/j.pain.2007.08.033

7. Kumar A, Kaur H, Singh A. Neuropathic pain models caused by damage to central or peripheral nervous system. Pharmacological Reports 2018; 70(2): 206–216. doi: 10.1016/j.pharep.2017.09.009

8. Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. PAIN® 2011; 152(1): 14–27. doi: 10.1016/j.pain.2010.07.031

9. Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Current Pain and Headache Reports 2018; 16(3): 191–198. doi: 10.1007/s11916-012-0256-0

10. Ossipov MH, Lai J, Malan TP, Porreca F. Spinal and supraspinal mechanisms of neuropathic pain. Annals of the New York Academy of Sciences 2000; 909(1): 12–24. doi: 10.1111/j.1749-6632.2000.tb06673.x

11. Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia 1998; 39(7): 677–686. doi: 10.1111/j.1528-1157.1998.tb01151.x

12. Woolf CJ, Bennett GJ, Doherty M, et al. Towards a mechanism-based classification of pain? Pain 1998; 77(3): 227–229. doi: 10.1016/S0304-3959(98)00099-2

13. Dworkin RH. An overview of neuropathic pain: Syndromes, symptoms, signs, and several mechanisms. The Clinical Journal of Pain 2002; 18(6): 343–349.

14. Cherry CL, Skolasky RL, Lal L, et al. Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort. Neurology 2006; 66(6): 867–873. doi: 10.1212/01.wnl.0000203336.12114.09

15. Murphy RA, Sunpath H, Kuritzkes DR, et al. Antiretroviral therapy — Associated toxicities in the resource-poor world: The challenge of a limited formulary. The Journal of Infectious Diseases 2007; 196(S3): S449–S456. doi: 10.1086/521112

16. Lund C, Koskinen M, Suneetha S, et al. Histopathological and clinical findings in leprosy patients with chronic neuropathic pain: A study from Hyderabad, India. Leprosy Review 2007; 78(4): 369–380. doi: 10.1086/521112

17. Lacoux P, Ford N. Treatment of neuropathic pain in Sierra Leone. The Lancet Neurology 2003; 1(3): 190–195. doi: 10.1016/S1474-4422(02)00075-3

18. Mijiyawa M, Oniankitan O, Kolani B, Koriko T. Low back pain in hospital outpatients in Lomé (Togo). Joint Bone Spine 2000; 67(6): 533–538. doi: 10.1016/S1297-319X(00)00204-9

19. Bennett MI, Attal N, Backonja MM, Baron R. Using screening tools to identify neuropathic pain. Pain 2007; 127(3): 199–203. doi: 10.1016/j.pain.2006.10.034

20. Freynhagen R, Baron R, Gockel U, Tölle TR. Pain DETECT: A new screening questionnaire to identify neuropathic components in patients with back pain. Current Medical Research and Opinion 2006; 22(10): 1911–1920. doi: 10.1185/030079906X132488

21. Daousi C, MacFarlane IA, Woodward A, et al. Chronic painful peripheral neuropathy in an urban community: A controlled comparison of people with and without diabetes. Diabetic Medicine 2004; 21(9): 976–982. doi: 10.1111/j.1464-5491.2004.01271.x

22. Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006; 29(7): 1518–1522. doi: 10.2337/dc05-2228

23. Galil K, Choo PW, Donahue JG. The sequelae of herpes zoster. Archives of Internal Medicine 1997; 157(11): 1209. doi: 10.1001/archinte.1997.00440320105010

24. Jung BF, Ahrendt GM, Oaklander AL, Dworkin RH. Neuropathic pain following breast cancer surgery: Proposed classification and research update. Pain 2003; 104(1–2): 1–13. doi: 10.1016/S0304-3959(03)00241-0

25. Jääskeläinen SK, Teerijoki-Oksa T, Virtanen A, et al. Sensory regeneration following intraoperatively verified trigeminal nerve injury. Neurology 2004; 62(11): 1951–1957. doi: 10.1212/01.wnl.0000129490.67954.c2

26. Hall GC, Carroll D, Parry D, McQuay HJ. Epidemiology and treatment of neuropathic pain: The UK primary care perspective. Pain 2006; 122(1–2): 156–162. doi: 10.1016/j.pain.2006.01.030

27. Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke pain. Pain 1995; 61(2): 187–193. doi: 10.1016/0304-3959(94)00144-4

28. Österberg A, Boivie J, Thuomas KÅ. Central pain in multiple sclerosis — Prevalence and clinical characteristics. European Journal of Pain 2005; 9(5): 531–531. doi: 10.1016/j.ejpain.2004.11.005

29. Finnerup N, Johannesen I, Sindrup S, et al. Pain and dysesthesia in patients with spinal cord injury: A postal survey. Spinal Cord 2001; 39(5): 256–262. doi: 10.1038/sj.sc.3101161

30. Max MB. Towards physiologically based treatment of patients with neuropathic pain. Pain 1990; 42(2): 131–133. doi: 10.1016/0304-3959(90)91156-D

31. Rowbotham MC, Petersen KL, Fields HL. Is postherpetic neuralgia more than one disorder? Pain Forum 1998; 7(4): 231–237. doi: 10.1016/S1082-3174(98)70003-0

32. Woolf CJ, Max MB. Mechanism-based pain diagnosis. The Journal of the American Society of Anesthesiologists 2001; 95(1): 241–249. doi: 10.1097/00000542-200107000-00034

33. May S, Serpell M. Diagnosis and assessment of neuropathic pain. F1000 Medicine Reports 2009; 1: 76. doi: 10.3410/m1-76

34. Gilron I, Baron R, Jensen T. Neuropathic pain: Principles of diagnosis and treatment. Mayo Clinic Proceedings 2015; 90(4): 532–545. doi: 10.1016/j.mayocp.2015.01.018

35. Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nature Reviews Disease Primers 2017; 3(1). doi: 10.1038/nrdp.2017.2

36. Rasmussen PV, Sindrup SH, Jensen TS, Bach FW. Symptoms and signs in patients with suspected neuropathic pain. Pain 2004; 110(1): 461–469. doi: 10.1016/j.pain.2004.04.034

37. Bouhassira D, Attal N. Diagnosis and assessment of neuropathic pain: The saga of clinical tools. Pain 2011; 152(3): S74–S83. doi: 10.1016/j.pain.2010.11.02

38. Attal N, Bouhassira D, Baron R. Diagnosis and assessment of neuropathic pain through questionnaires. The Lancet Neurology 2018; 17(5): 456–466. doi: 10.1016/S1474-4422(18)30071-1

39. Bouhassira D. Neuropathic pain: Definition, assessment and epidemiology. Revue Neurologique 2019; 175(1–2): 16–25. doi: 10.1016/j.neurol.2018.09.016

40. Freynhagen R, Tölle TR, Gockel U, Baron R. The painDETECT project — Far more than a screening tool on neuropathic pain. Current Medical Research and Opinion 2016; 32(6): 1033–1057. doi: 10.1185/03007995.2016.1157460

41. Bhatnagar S, Mishra S, Roshni S, et al. Neuropathic pain in cancer patients — Prevalence and management in a tertiary care anesthesia-run referral clinic based in urban India. Journal of palliative medicine 2010; 13(7): 819–824. doi: 10.1089/jpm.2009.0405

42. Yawn BP, Wollan PC, Weingarten TN, et al. The prevalence of neuropathic pain: Clinical evaluation compared with screening tools in a community population. Pain Medicine 2009; 10(3): 586–593. doi: 10.1111/j.1526-4637.2009.00588.x

43. Dubuisson D, Melzack R. Psychology classification of clinical pain descriptions by multiple group discriminant analysis. Pain 1976; 2(4): 444–445. doi: 10.1016/0304-3959(76)90099-3

44. Dubuisson D, Melzack R. Classification of clinical pain descriptions by multiple group discriminant analysis. Experimental Neurology 1976; 51(2): 480–487. doi: 10.1016/0014-4886(76)90271-5

45. Melzack R, Terrence C, Fromm G, Amsel R. Trigeminal neuralgia and atypical facial pain: Use of the McGill pain questionnaire for discrimination and diagnosis. Pain 1986; 27(3): 297–302. doi: 10.1016/0304-3959(86)90157-0

46. Masson EA, Hunt L, Gem JM, Boulton AJM. A novel approach to the diagnosis and assessment of symptomatic diabetic neuropathy. Pain 1989; 38(1): 25–28. doi: 10.1016/0304-3959(89)90068-7

47. Boureau F, Doubrere JF, Luu M. Study of verbal description in neuropathic pain. Pain 1990; 42(2): 145–152. doi: 10.1016/0304-3959(90)91158-F

48. Han HC, Lee DH, Chung JM. Characteristics of ectopic discharges in a rat neuropathic pain model. PAIN® 2000; 84(2–3): 253–261. doi: 10.1016/S0304-3959(99)00219-5

49. Koltzenburg M, Scadding J. Neuropathic pain. Current Opinion in Neurology 2001; 14(5): 641–647. doi: 10.1097/00019052-200110000-00014

50. Rosenthal P, Borsook D. Ocular neuropathic pain. British Journal of Ophthalmology 2015; 100(1): 128–134. doi: 10.1136/bjophthalmol-2014-306280

51. Baron R. Neuropathic pain: A clinical perspective. In: Canning BJ, Spina D (editors). Sensory Nerves. Springer; 2009. Volume 194. pp. 3–30.

52. Baron R. Mechanisms of disease: Neuropathic pain — A clinical perspective. Nature clinical practice Neurology 2006; 2(2): 95–106. doi: 10.1038/ncpneuro0113

53. Klein T, Magerl W, Rolke R, Treede RD. Human surrogate models of neuropathic pain. Pain 2005; 115(3): 227–233. doi: 10.1016/j.pain.2005.03.021

54. Freynhagen R, Baron R, Tölle T, 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): 529–537. doi: 10.1185/030079906x89874

55. Attal N, Cruccu G, Haanpää M, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. European journal of neurology 2006; 13(11): 1153–1169. doi: 10.1111/j.1468-1331.2006.01511.x

56. Watanabe Y, Saito H, Abe K. Tricyclic antidepressants block NMDA receptor-mediated synaptic responses and induction of long-term potentiation in rat hippocampal slices. Neuropharmacology 1993; 32(5): 479–486. doi: 10.1016/0028-3908(93)90173-Z

57. Hall H, Sven-Ove Ö. Effects of antidepressant drugs on different receptors in the brain. European Journal of Pharmacology 1981: 70(3): 393–407. doi: 10.1016/0014-2999(81)90172-2

58. Shlay JC, Chaloner K, Max MB, et al. Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: A randomized controlled trial. JAMA 1998; 280(18): 1590–1595. doi: 10.1001/jama.280.18.1590

59. Berger A, Dukes E, Mercadante S, Oster G. Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain. European Journal of Cancer Care 2006; 15(2): 138–145. doi: 10.1111/j.1365-2354.2005.00624.x

60. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: An overview of recent guidelines. The American Journal of Medicine 2009; 122(10): S22–S32. doi: 10.1016/j.amjmed.2009.04.007

61. Cai Z, McCaslin PP. Amitriptyline, desipramine, cyproheptadine and carbamazepine, in concentrations used therapeutically, reduce kainate-and N-methyl-D-aspartate-induced intracellular Ca2+ levels in neuronal culture. European Journal of Pharmacology 1992; 219(1): 53–57. doi: 10.1016/0014-2999(92)90579-S

62. Reynolds IJ, Miller RJ. Tricyclic antidepressants block N-methyl-D-aspartate receptors: similarities to the action of zinc. British Journal of Pharmacology 1988; 95(1): 95–102. doi: 10.1111/j.1476-5381.1988.tb16552.x

63. Barnet CS, Tse JY, Kohane DS. Site 1 sodium channel blockers prolong the duration of sciatic nerve blockade from tricyclic antidepressants. Pain 2004; 110(1): 432–438. doi: 10.1016/j.pain.2004.04.027

64. Lavoie PA, Beauchamp G, Elie R. Tricyclic antidepressants inhibit voltage-dependent calcium channels and Na+–Ca2+ exchange in rat brain cortex synaptosomes. Canadian Journal of Physiology and Pharmacology 1990; 68(11): 1414–1418. doi: 10.1139/y90-215

65. Jurjević A. Painful diabetic polyneuropathy. Rad Hrvatske akademije znanosti i umjetnosti. Medicinske znanosti 2009; 504(33): 105–108.

66. Calabrò RS, Bramanti P. Pregabalin-induced severe delayed ejaculation. Epilepsy & Behavior 2010; 19(3): 543. doi: 10.1016/j.yebeh.2010.07.026

67. Melkani I, Kumar B, Panchal S, et al. Comparison of sildenafil, fluoxetine and its co-administration against chronic constriction injury induced neuropathic pain in rats: An influential additive effect. Neurological Research 2019; 41(10): 875–882. doi: 10.1080/01616412.2019.1630091

68. Devi P, Madhu K, Ganapathy B, et al. Evaluation of efficacy and safety of gabapentin, duloxetine, and pregabalin in patients with painful diabetic peripheral neuropathy. Indian Journal of Pharmacology 2012; 44(1): 51–56. doi: 10.4103/0253-7613.91867

69. Dauri M, Faria S, Gatti A, et al. Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences. Current Drug Targets 2009; 10(8): 716–733. doi: 10.2174/138945009788982513

70. Singh D, Kennedy DH. The use of gabapentin for the treatment of postherpetic neuralgia. Clinical Therapeutics 2003; 25(3): 852–889. doi: 10.1016/S0149-2918(03)80111-X

71. Simpson DM, McArthur JC, Olney R, et al. Lamotrigine for HIV-associated painful sensory neuropathies: A placebo-controlled trial. Neurology 2003; 60(9): 1508–1514. doi: 10.1212/01.wnl.0000063304.88470.d9

72. Silver M, Blum D, Grainger J, 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): 446–454. doi: 10.1016/j.jpainsymman.2006.12.015

73. Vestergaard K, Andersen G, Gottrup H, et al. Lamotrigine for central poststroke pain: A randomized controlled trial. Neurology 2001; 56(2): 184–190. doi: 10.1212/wnl.56.2.184

74. Finnerup NB, Sindrup SH, Bach FW, et al. Lamotrigine in spinal cord injury pain: A randomized controlled trial. Pain 2002; 96(3): 375–383. doi: 10.1016/S0304-3959(01)00484-5

75. Wiffen PJ, Derry S, Lunn MP, Moore RA. Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2013. doi: 10.1002/14651858.cd008314.pub2

76. Eisenberg E, McNicol ED, Carr DB. Opioids for neuropathic pain. Cochrane Database of Systematic Reviews 2006. doi:10.1002/14651858.cd006146

77. Watson PCN, Moulin D, Watt-Watson J, et al. Controlled-release oxycodone relieves neuropathic pain: A randomized controlled trial in painful diabetic neuropathy. Pain 2003; 105(1–2): 71–78. doi: 10.1016/S0304-3959(03)00160-X

78. Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: An overview and literature update. Mayo Clin Proceedings 2010; 85(3s): S3–14. doi: 10.4065/mcp.2009.0649

79. Ballantyne JC. Opioid analgesia: Perspectives on right use and utility. Pain Physician 2007; 10(3): 479–491. doi: 10.36076/ppj.2007/10/479

80. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: A Cochrane review. Journal of Neurology, Neurosurgery & Psychiatry 2010; 81(12): 1372–1373. doi: 10.1136/jnnp.2008.144964

81. Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Neurology 2002; 59(5 suppl 2): S14–S17. doi: 10.1212/WNL.59.5_suppl_2.S14

82. Tremont-Lukats IW, Megeff C, Backonja MM. Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. Drugs 2000; 60(5): 1029–1052. doi: 10.2165/00003495-200060050-00005.

83. Blom S. Trigeminal neuralgia: Its treatment with a new anticonvulsant drug (G-32883). The Lancet 1962; 279(7234): 839–840. doi: 10.1016/s0140-6736(62)91847-0

84. Abedpoor N, Taghian F, Hajibabaie F. Cross brain-gut analysis highlighted hub genes and LncRNA networks differentially modified during leucine consumption and endurance exercise in mice with depression-like behaviors. Molecular Neurobiology 2022; 59(7): 4106–4123. doi: 10.1007/s12035-022-02835-1

85. Balanaser M, Carley M, Baron R, et al. Combination pharmacotherapy for the treatment of neuropathic pain in adults: Systematic review and meta-analysis. Pain 2022; 164(2): 230–251. doi: 10.1097/j.pain.0000000000002688

86. Gilron I, Bailey JM, Tu D, et al. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: A double-blind, randomised controlled crossover trial. The Lancet 2009; 374(9697): 1252–1261. doi: 10.1016/S0140-6736(09)61081-3

87. Raffa RB, Pergolizzi JV, Segarnick DJ, Tallarida RJ. Oxycodone combinations for pain relief. Drugs of today (Barcelona, Spain: 1998) 2010; 46(6): 379–98. doi: 10.1358/dot.2010.46.6.1470106

88. Eisenberg E, Suzan E. Drug combinations in the treatment of neuropathic pain. Current Pain and Headache Reports 2014; 18: 463. doi: 10.1007/s11916-014-0463-y

89. Amr YM. 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): 245–249. doi: 10.36076/ppj.2010/13/245

90. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: A randomized controlled trial. JAMA 1998; 280(21): 1831–1836.

91. Rowbotham M, Harden N, Stacey B, et al. Gabapentin for the treatment of postherpetic neuralgia: A randomized controlled trial. JAMA 1998; 280(21): 1837–1842. doi: 10.1001/jama.280.21.1837

92. Portenoy RK. Treatment of cancer pain. The Lancet 2011; 377(9784): 2236–2247. doi: 10.1016/S0140-6736(11)60236-5

93. NICE. Neuropathic Pain: The Pharmacological Management of Neuropathic Pain in Adults in Non-Specialist Settings. National Institute for Health and Clinical Excellence; 2010.

94. Sultan A, Gaskell H, Derry S, Moore RA. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: Systematic review of randomised trials. BMC Neurology 2008; 8(1): 1–9. doi: 10.1186/1471-2377-8-29

95. Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2011. doi: 10.1002/14651858.CD009318.pub2

96. Moore RA, Wiffen PJ, Derry S, Rice ASC. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014. doi: 10.1002/14651858.cd007938.pub3

97. Moore RA, Straube S, Wiffen PJ, et al. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews 2009. doi: 10.1002/14651858.cd007076.pub2

98. Derry S, Rice AS, Cole P, et al. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2017. doi: 10.1002/14651858.cd007393.pub4

99. Kalso E, Aldington DJ, Moore RA. Drugs for neuropathic pain. BMJ 2013; 347. doi: 10.1136/bmj.f7339

100. Stilling RM, Dinan TG, Cryan JF. Cryan, microbial genes, brain & behaviour — Epigenetic regulation of the gut-brain axis. Genes, Brain and Behavior 2014; 13(1): 69–86. doi: 10.1111/gbb.12109

101. Clapp M, Aurora N, Herrera L, et al. Gut microbiota’s effect on mental health: The gut-brain axis. Clinics and Practice 2017; 7(4): 987. doi: 10.4081/cp.2017.987

102. Günther C, Rothhammer V, Karow M, et al. The gut-brain axis in inflammatory bowel disease — Current and future perspectives. International Journal of Molecular Sciences 2021; 22(16): 8870. doi: 10.3390/ijms22168870

103. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464(7285): 59–65. doi: 10.1038/nature08821

104. Finnerup NB, Haroutounian S, Kamerman P, et al. Neuropathic pain: An updated grading system for research and clinical practice. Pain 2016; 157(8): 1599–1606. doi: 10.1097/j.pain.0000000000000492

105. De Palma G, Collins SM, Bercik P, Verdu EF. The microbiota-gut-brain axis in gastrointestinal disorders: Stressed bugs, stressed brain or both? The Journal of Physiology 2014; 592(14): 2989–2997. doi: 10.1113/jphysiol.2014.273995

106. Hyland N, Stanton C. The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota. Academic Press; 2016.

107. Kaur M, Singh A, Kumar B, et al. Protective effect of co-administration of curcumin and sildenafil in alcohol induced neuropathy in rats. European Journal of Pharmacology 2017; 805: 58–66. doi: 10.1016/j.ejphar.2017.03.012

108. Dinan TG, Cryan JF. The microbiome-gut-brain axis in health and disease. Gastroenterology Clinics 2017; 46(1): 77–89. doi: 10.1016/j.gtc.2016.09.007

109. Defaye M, Gervason S, Altier C, et al. Microbiota: A novel regulator of pain. Journal of Neural Transmission 2019; 127(4): 445–465. doi: 10.1007/s00702-019-02083-z

110. Kumar B, Singh SK, Prakash T, et al. Pharmacokinetic and pharmacodynamic evaluation of solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats. Neurological Sciences 2021; 42(5): 1785–1797. doi: 10.1007/s10072-020-04628-7

111. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nature Reviews Microbiology 2012; 10(11): 735–742. doi: 10.1038/nrmicro2876

112. Montiel-Castro AJ, González-Cervantes RM, Bravo-Ruiseco G, Pacheco-López G. The microbiota-gut-brain axis: Neurobehavioral correlates, health and sociality. Frontiers in Integrative Neuroscience 2014; 54(7): 938–956. doi: 10.1080/10408398.2011.619671

113. Ashraf R, Shah NP. Immune system stimulation by probiotic microorganisms. Critical Reviews in Food Science and Nutrition 2014; 54(7): 938–956. doi: 10.1080/10408398.2011.619671

114. Vagnerová K, Vodička M, Hermanová P, et al. Interactions between gut microbiota and acute restraint stress in peripheral structures of the hypothalamic-pituitary-adrenal axis and the intestine of male mice. Frontiers in Immunology 2019: 10. doi: 10.3389/fimmu.2019.02655

115. Foster JA, Baker GB, Dursun SM. The relationship between the gut microbiome-immune system-brain axis and major depressive disorder. Frontiers in Neurology 2021: (12). doi: 10.3389/fneur.2021.721126

116. Morais LH, Schreiber HL, Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders. Nature Reviews Microbiology 2020; 19(4): 241–255. doi: 10.1038/s41579-020-00460-0

117. Morton GJ, Cummings DE, Baskin DG, et al. Central nervous system control of food intake and body weight. Nature 2006; 443(7109): 289–295. doi: 10.1038/nature05026

118. Könner AC, Klöckener T, Brüning JC. Control of energy homeostasis by insulin and leptin: Targeting the arcuate nucleus and beyond. Physiology & behavior 2009; 97(5): 632–638. doi: 10.1016/j.physbeh.2009.03.027

119. Broadwell RD, Brightman MW. Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood. Journal of Comparative Neurology 1976; 166(3): 257–283. doi: 10.1002/cne.901660302

120. Peruzzo B, Pastor FE, Blázquez JL, et al. A second look at the barriers of the medial basal hypothalamus. Experimental Brain Research 2000; 132(1): 10–26. doi: 10.1007/s002219900289

121. Kalra SP, Dube MG, Pu S, et al. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrine Reviews 1999; 20(1): 68–100. doi: 10.1210/er.20.1.68

122. Bouret SG, Draper SJ, Simerly RB. Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice. Journal of Neuroscience 2004; 24(11): 2797–2805. doi: 10.1523/jneurosci.5369-03.2004

123. Blevins JE, Baskin DG. Hypothalamic-brainstem circuits controlling eating. Forum of Nutrition 2010; 63: 133–140. doi: 10.1159/000264401

124. Grill HJ, Schwartz MW, Kaplan JM, et al. Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 2002; 143(1): 239–246. doi: 10.1210/endo.143.1.8589

125. Lebrun B, Bariohay B, Moyse E, Jean A. Brain-derived neurotrophic factor (BDNF) and food intake regulation: A minireview. Autonomic Neuroscience 2006; 126: 30–38. doi: 10.1016/j.autneu.2006.02.027

126. Chaudhri O, Small C, Bloom S. Gastrointestinal hormones regulating appetite. Philosophical Transactions of the Royal Society B: Biological Sciences 2006; 361(1471): 1187–1209. doi: 10.1098/rstb.2006.1856

127. Schwartz GJ. The role of gastrointestinal vagal afferents in the control of food intake: Current prospects. Nutrition 2000; 16(10): 866–873. doi: 10.1016/s0899-9007(00)00464-0

128. Price CJ, Hoyda TD, Ferguson AV. The area postrema: A brain monitor and integrator of systemic autonomic state. The Neuroscientist 2007; 14(2): 182–194. doi: 10.1177/1073858407311100

129. Ter Horst GJ, De Boer P, Luiten PGM, et al. Ascending projections from the solitary tract nucleus to the hypothalamus. A Phaseolus vulgaris lectin tracing study in the rat. Neuroscience 1989; 31(3): 785–797. doi: 10.1016/0306-4522(89)90441-7

130. Ter Horst GJ, Luiten PGM, Kuipers F. Descending pathways from hypothalamus to dorsal motor vagus and ambiguus nuclei in the rat. Journal of the Autonomic Nervous System 1984; 11(1): 59–75. doi: 10.1016/0165-1838(84)90008-0

131. Grijalva CV, Novin D. The role of the hypothalamus and dorsal vagal complex in gastrointestinal function and pathophysiology. Annals of the New York Academy of Sciences 1990; 597: 207–222. doi: 10.1111/j.1749-6632.1990.tb16169.x

132. Riediger T, Zuend D, Becskei C, Lutz TA. The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis. American Journal of Physiology-Regulatory 2004; 286(1): R114-R122. doi: 10.1152/ajpregu.00333.2003

133. Gribble FM, Reimann F. Enteroendocrine cells: Chemosensors in the intestinal epithelium. Annual Review of Physiology 2016; 78(1): 277–299. doi: 10.1146/annurev-physiol-021115-105439

134. Worthington JJ, Reimann F, Gribble FM. Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity. Mucosal Immunology 2018; 11(1): 3–20. doi: 10.1038/mi.2017.73

135. Guarner F, Khan AG, Garisch J, et al. World gastroenterology organisation global guidelines: Probiotics and prebiotics october 2011. Journal of Clinical Gastroenterology 2012; 46(6): 468–481. doi: 10.1097/mcg.0b013e3182549092

136. Delgado TC. Glutamate and GABA in appetite regulation. Frontiers in Endocrinology 2013; 4. doi: 10.3389/fendo.2013.00103

137. Meng F, Han Y, Srisai D, et al. New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism. Proceedings of the National Academy of Sciences 2016; 113(13): 3645–3650. doi: 10.1073/pnas.1602049113

138. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Research 2018; 1693: 128–133. doi: 10.1016/j.brainres.2018.03.015

139. Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PloS One 2012; 7(4): e34938. doi: 10.1371/journal.pone.0034938

140. Moberg LJ, Sugiyama H. Microbial ecological basis of infant botulism as studied with germfree mice. Infection and Immunity 1979; 25(2): 653–657. doi: 10.1128/iai.25.2.653-657.1979

141. Sullivan NM, Mills DC, Riemann HP, Arnon SS. Inhibition of growth of Clostridium botulinum by intestinal microflora isolated from healthy infants. Microbial Ecology in Health and Disease 1988; 1(3): 179–192. doi: 10.3109/08910608809141534

142. Borriello SP, Barclay FE. An in-vitro model of colonisation resistance to Clostridium difficile infection. Journal of Medical Microbiology 1986; 21(4): 299–309. doi: 10.1099/00222615-21-4-299.

143. Wilson K, Moore L, Patel M, Permoad P. Suppression of potential pathogens by a defined colonic microflora. Microbial Ecology in Health and Disease 1988; 1(4): 237–243. doi: 10.3109/08910608809140528

144. Syed SA, Abrams GD, Freter R. Efficiency of various intestinal bacteria in assuming normal functions of enteric flora after association with germ-free mice. Infection and Immunity 1970; 2(4): 376–386. doi: 10.1128/iai.2.4.376-386.1970

145. Pongpech P, Hentges DJ. Inhibition of shigella sonnei and enterotoxigenic Escherichia coli by volatile fatty acids in mice. Microbial Ecology in Health and Disease 1989; 2(3): 153–161. doi: 10.3109/08910608909140213

146. Fuller R. Probiotics in human medicine. Gut 1991; 32(4): 439–442. doi: 10.1136/gut.32.4.439

147. Verma V, Singh N, Jaggi A. Pregabalin in neuropathic pain: Evidences and possible mechanisms. Current Neuropharmacology 2014; 12(1): 44–56. doi: 10.2174/1570159x1201140117162802

148. Vink S, Alewood P. Targeting voltage‐gated calcium channels: Developments in peptide and small‐molecule inhibitors for the treatment of neuropathic pain. British Journal of Pharmacology 2012; 167(5): 970–989. doi: 10.1111/j.1476-5381.2012.02082.x

149. Kurshan PT. The Role of Alpha2delta-3 in Calcium-Channel Localization, Synaptic Function and Bouton Formation. Harvard University; 2010.

150. Wykes RCE, Bauer CS, Khan SU, et al. Differential regulation of endogenous N-and P/Q-type Ca2+ channel inactivation by Ca2+/calmodulin impacts on their ability to support exocytosis in chromaffin cells. Journal of Neuroscience 2007; 27(19): 5236–5248. doi: 10.1523/jneurosci.3545-06.2007

151. Wilkinson KA. Molecular determinants of mechanosensation in the muscle spindle. Current Opinion in Neurobiology 2022; 74: 102542. doi: 10.1016/j.conb.2022.102542

152. Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiological Reviews 2019; 99(4): doi: 10.1152/physrev.00018.2018

153. Sajman J, Trus M, Atlas D, Sherman E. The L-type voltage-gated calcium channel co-localizes with Syntaxin 1A in nano-clusters at the plasma membrane. Scientific Reports 2017; 7(1): 11350. doi: 10.1038/s41598-017-10588-4

154. Marvin JS, Borghuis BG, Tian L, et al. An optimized fluorescent probe for visualizing glutamate neurotransmission. Nature Methods 2013; 10(2): 162–170. doi: 10.1038/nmeth.2333

155. Mallick HN. Understanding safety of glutamate in food and brain. Indian Journal of Physiology and Pharmacology 2007; 51(3): 216–234.

156. Huang C, Huang C, Wu S. The opening effect of pregabalin on atp-sensitive potassium channels in differentiated hippocampal neuron-derived H19‐7 cells. Epilepsia 2006; 47(4): 720–726. doi: 10.1111/j.1528-1167.2006.00498.x

157. Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nature Reviews Immunology 2013; 13(5): 321–335. doi: 10.1038/nri3430

158. Bouskra D, Brézillon C, Bérard M, et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 2008; 456(7221): 507–510. doi: 10.1038/nature07450

159. Wang Y, Begum-Haque S, Telesford KM, et al. A commensal bacterial product elicits and modulates migratory capacity of CD39+CD4 T regulatory subsets in the suppression of neuroinflammation. Gut Microbes 2014; 5(4): 552–561. doi: 10.4161/gmic.29797

160. Al‐Hassi HO, Mann ER, Sanchez B, et al. Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Molecular Nutrition & Food Research 2013; 58(5): 1132–1143. doi: 10.1002/mnfr.201300596

161. Gupta V, Garg R. Probiotics. Indian Journal of Medical Microbiology 2009; 27(3): 202–209. doi: 10.4103/0255-0857.53201

162. Williams NT. Probiotics. American Journal of Health-System Pharmacy 2010; 67(6): 449–458. doi: 10.2146/ajhp090168

163. Tan FHP, Liu G, Lau SYA, et al. Lactobacillus probiotics improved the gut microbiota profile of a Drosophila melanogaster Alzheimer’s disease model and alleviated neurodegeneration in the eye. Beneficial Microbes 2020; 11(1): 79–89. doi: 10.3920/bm2019.0086

164. Khalighi A, Behdani R, Kouhestani S. Probiotics: A comprehensive review of their classification, mode of action and role in human nutrition. Probiotics and Prebiotics in Human Nutrition and Health 2016. doi: 10.5772/63646

165. Lee ES, Song EJ, Nam YD, Lee SY. Probiotics in human health and disease: From nutribiotics to pharmabiotics. Journal of Microbiology 2018; 56(11): 773–782. doi: 10.1007/s12275-018-8293-y

166. Fernández M, Hudson JA, Korpela R, et al. Impact on human health of microorganisms present in fermented dairy products: an overview. BioMed Research International 2015; 2015: 1–13. doi: 10.1155/2015/412714

167. Alzheimer’s Association. Alzheimer’s and Dementia in India. Available online: https://www.alz.org/in/dementia-alzheimers-en.asp (accessed on 2 November 2023).

168. Abdelrahman KM, Hackshaw KV. Nutritional supplements for the treatment of neuropathic pain. Biomedicines 2021; 9(6): 674. doi: 10.3390/biomedicines9060674

169. Tong X, Dong JY, Wu ZW, et al. Dairy consumption and risk of type 2 diabetes mellitus: A meta-analysis of cohort studies. European Journal of Clinical Nutrition 2011; 65(9): 1027–1031. doi: 10.1038/ejcn.2011.62

170. Mozaffarian D, Hao T, Rimm EB, et al. Changes in diet and lifestyle and long-term weight gain in women and men. New England Journal of Medicine 2011; 364(25): 2392–2404. doi: 10.1056/nejmoa1014296

171. Biron CA. Role of early cytokines, including alpha and beta interferons (IFN-αβ), in innate and adaptive immune responses to viral infections. Seminars in Immunology 1998; 10(5): 383–390. doi: 10.1006/smim.1998.0138

172. Gately MK, Renzetti LM, Magram J, et al. The interleukin-12/interleukin-12-receptor system: Role in normal and pathologic immune responses. Annual Review of Immunology 1998; 16(1): 495–521. doi: 10.1146/annurev.immunol.16.1.495

173. Mocellin S, Panelli MC, Wang E, et al. The dual role of IL-10. Trends in Immunology 2003; 24(1): 36–43. doi: 10.1016/S1471-4906(02)00009-1

174. Mocellin S, Panelli MC, Wang E, et al. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990; 249(4975): 1431–1433. doi: 10.1126/science.1698311

175. Mendoza L. Potential effect of probiotics in the treatment of breast cancer. Oncology Reviews 2019; 13(2). doi: 10.4081/oncol.2019.422

176. Elangovan A, Allegretti JR, Fischer M. Microbiota modulation-based therapy for luminal GI disorders: Current applications of probiotics and fecal microbiota transplantation. Expert Opinion on Biological Therapy 2019; 19(12): 1343–1355. doi: 10.1080/14712598.2019.1673725

177. Homayouni A, Bagheri N, Mohammad-Alizadeh-Charandabi S, et al. Prevention of gestational diabetes mellitus (GDM) and probiotics: Mechanism of action: A review. Current Diabetes Reviews 2020; 16(6): 538–545. doi: 10.2174/1573399815666190712193828

178. Dale HF, Rasmussen SH, Asiller ÖÖ, Lied GA. Probiotics in irritable bowel syndrome: An up-to-date systematic review. Nutrients 2019; 11(9): 2048. doi: 10.3390/nu11092048

179. Toma W, Kyte SL, Bagdas D, et al. Effects of paclitaxel on the development of neuropathy and affective behaviors in the mouse. Neuropharmacology 2017; 117: 305–315. doi: 10.1016/j.neuropharm.2017.02.020

180. Castelli V, Palumbo P, d’Angelo M, et al. Probiotic DSF counteracts chemotherapy induced neuropathic pain. Oncotarget 2018; 9(46): 27998–28008. doi: 10.18632/oncotarget.25524

181. Cuozzo M, Castelli V, Avagliano C, et al. Effects of chronic oral probiotic treatment in paclitaxel-induced neuropathic pain. Biomedicines 2021; 9(4): 346. doi: 10.3390/biomedicines9040346

182. Bonfili L, Cecarini V, Cuccioloni M, et al. SLAB51 probiotic formulation activates SIRT1 pathway promoting antioxidant and neuroprotective effects in an AD mouse model. Molecular Neurobiology 2018; 55(10): 7987–8000. doi: 10.1007/s12035-018-0973-4

183. Shabani M, Hasanpour E, Mohammadifar M, et al. Evaluating the effects of probiotic supplementation on neuropathic pain and oxidative stress factors in an animal model of chronic constriction injury of the sciatic nerve. Basic and Clinical Neuroscience 2023; 14(3): 375–384. doi: 10.32598/bcn.2022.3772.1

184. Chen KH, Lin HS, Li YC, et al. Synergic effect of early administration of probiotics and adipose-derived mesenchymal stem cells on alleviating inflammation-induced chronic neuropathic pain in rodents. International Journal of Molecular Sciences 2022; 23(19): 11974. doi: 10.3390/ijms231911974

185. Lee J, Lee G, Ko G, et al. Nerve injury-induced gut dysbiosis contributes to spinal cord TNF-α expression and nociceptive sensitization. Brain, Behavior, and Immunity 2023; 110: 155–161. doi: 10.1016/j.bbi.2023.03.005

186. WANG H, LI S, LI H, et al. Mechanism of probiotic VSL# 3 inhibiting NF-κB and TNF-α on colitis through TLR4-NF-κB signal pathway. Iranian Journal of Public Health 2019; 48(7): 1292–1300.

187. Hsieh TH, Kuo CW, Hsieh KH, et al. Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson’s disease. Brain Sciences 2020; 10(4): 206. doi: 10.3390/brainsci10040206

188. Wu H, Zhang W, Huang M, et al. Prolonged high-fat diet consumption throughout adulthood in mice induced neurobehavioral deterioration via gut-brain axis. Nutrients 2023; 15(2): 392. doi: 10.3390/nu15020392

189. Snelson M, Coughlan M. Dietary advanced glycation end products: Digestion, metabolism and modulation of gut microbial ecology. Nutrients 2019; 11(2): 215. doi: 10.3390/nu11020215

190. Ghanbari F, Abedpoor N, Peymani M, et al. Effects of the phytocompound combination against dysbiosis induced by AGE-rich High-fat diet in mice. International Journal of Medical Laboratory 2023; 10(2). doi: 10.18502/ijml.v10i2.12948

191. Hajibabaie F, Abedpoor N, Safavi K, Taghian F. Natural remedies medicine derived from flaxseed (secoisolariciresinol diglucoside, lignans, and α‐linolenic acid) improve network targeting efficiency of diabetic heart conditions based on computational chemistry techniques and pharmacophore modeling. Journal of Food Biochemistry 2022; 46(12). doi: 10.1111/jfbc.14480

192. Akbarian F, Rahmani M, Tavalaee M, et al. Effect of different high-fat and advanced glycation end-products diets in obesity and diabetes-prone C57BL/6 mice on sperm function. International Journal of Fertility & Sterility 2021; 15(3): 226–233. doi: 10.22074/IJFS.2021.137231.1022

193. Hajibabaie F, Aali F, Abedpoor N. Pathomechanisms of non-coding RNAs and hub genes related to the oxidative stress in diabetic complications. F1000Research 2023; 11: 1132. doi: 10.12688/f1000research.125945.2