DOI QR코드

DOI QR Code

Targeting nerve growth factor for pain relief: pros and cons

  • Sahar Jaffal (Department of Biotechnology and Genetic Engineering, Faculty of Science, Philadelphia University) ;
  • Raida Khalil (Department of Biotechnology and Genetic Engineering, Faculty of Science, Philadelphia University)
  • 투고 : 2024.07.22
  • 심사 : 2024.09.02
  • 발행 : 2024.10.01

초록

Nerve growth factor (NGF) is a neurotrophic protein that has crucial roles in survival, growth and differentiation. It is expressed in neuronal and non-neuronal tissues. NGF exerts its effects via two types of receptors including the high affinity receptor, tropomyosin receptor kinase A and the low affinity receptor p75 neurotrophin receptor highlighting the complex signaling pathways that underlie the roles of NGF. In pain perception and transmission, multiple studies shed light on the effects of NGF on different types of pain including inflammatory, neuropathic, cancer and visceral pain. Also, the binding of NGF to its receptors increases the availability of many nociceptive receptors such as transient receptor potential vanilloid 1, transient receptor potential ankyrin 1, N-methyl-D-aspartic acid, and P2X purinoceptor 3 as well as nociceptive transmitters such as substance P and calcitonin gene-related peptide. The role of NGF in pain has been documented in pre-clinical and clinical studies. This review aims to shed light on the role of NGF and its signaling in different types of pain.

키워드

과제정보

This review was published with the support of the Deanship of Scientific Research and Graduate Studies at Philadelphia University, Amman, Jordan.

참고문헌

  1. Levi-Montalcini R, Angeletti PU. Essential role of the nerve growth factor in the survival and maintenance of dissociated sensory and sympathetic embryonic nerve cells in vitro. Dev Biol 1963; 6: 653-9. 
  2. Chang DS, Hsu E, Hottinger DG, Cohen SP. Anti-nerve growth factor in pain management: current evidence. J Pain Res 2016; 9: 373-83. 
  3. Yuan H, Du S, Chen L, Xu X, Wang Y, Ji F. Hypomethylation of nerve growth factor (NGF) promotes binding of C/EBPα and contributes to inflammatory hyperalgesia in rats. J Neuroinflammation 2020; 17: 34. 
  4. Bennett DL. Neurotrophic factors: important regulators of nociceptive function. Neuroscientist 2001; 7: 13-7. 
  5. Hefti FF, Rosenthal A, Walicke PA, Wyatt S, Vergara G, Shelton DL, et al. Novel class of pain drugs based on antagonism of NGF. Trends Pharmacol Sci 2006; 27: 85-91. 
  6. Crowley C, Spencer SD, Nishimura MC, Chen KS, Pitts-Meek S, Armanini MP, et al. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 1994; 76: 1001-11. 
  7. Schmelz M, Mantyh P, Malfait AM, Farrar J, Yaksh T, Tive L, et al. Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety. Pain 2019; 160: 2210-20. 
  8. Osikowicz M, Longo G, Allard S, Cuello AC, Ribeiroda-Silva A. Inhibition of endogenous NGF degradation induces mechanical allodynia and thermal hyperalgesia in rats. Mol Pain 2013; 9: 37. Erratum in: Mol Pain 2013; 9: 55. 
  9. Price TJ, Flores CM. Critical evaluation of the colocalization between calcitonin gene-related peptide, substance P, transient receptor potential vanilloid subfamily type 1 immunoreactivities, and isolectin B4 binding in primary afferent neurons of the rat and mouse. J Pain 2007; 8: 263-72. 
  10. Truzzi F, Marconi A, Lotti R, Dallaglio K, French LE, Hempstead BL, et al. Neurotrophins and their receptors stimulate melanoma cell proliferation and migration. J Invest Dermatol 2008; 128: 2031-40. 
  11. Ricci A, Salvucci C, Castelli S, Carraturo A, de Vitis C, D'Ascanio M. Adenocarcinomas of the lung and neurotrophin system: a review. Biomedicines 2022; 10: 2531. 
  12. Hirose M, Kuroda Y, Murata E. NGF/TrkA signaling as a therapeutic target for pain. Pain Pract 2016; 16: 175-82. 
  13. Wise BL, Seidel MF, Lane NE. The evolution of nerve growth factor inhibition in clinical medicine. Nat Rev Rheumatol 2021; 17: 34-46. 
  14. Denk F, Bennett DL, McMahon SB. Nerve growth factor and pain mechanisms. Annu Rev Neurosci 2017; 40: 307-25. 
  15. Zhang X, Huang J, McNaughton PA. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 2005; 24: 4211-23. 
  16. Oo WM, Hunter DJ. Nerve growth factor (NGF) inhibitors and related agents for chronic musculoskeletal pain: a comprehensive review. BioDrugs 2021; 35: 611-41. 
  17. Barker PA, Mantyh P, Arendt-Nielsen L, Viktrup L, Tive L. Nerve growth factor signaling and its contribution to pain. J Pain Res 2020; 13: 1223-41. 
  18. Vera DB, Fredes AN, Garrido MP, Romero C. Role of mitochondria in interplay between NGF/TRKA, miR-145 and possible therapeutic strategies for epithelial ovarian cancer. Life (Basel) 2021; 12: 8. 
  19. Iftinca M, Defaye M, Altier C. TRPV1-targeted drugs in development for human pain conditions. Drugs 2021; 81: 7-27. 
  20. Shane Anderson A, Loeser RF. Why is osteoarthritis an age-related disease? Best Pract Res Clin Rheumatol 2010; 24: 15-26. 
  21. Molloy NH, Read DE, Gorman AM. Nerve growth factor in cancer cell death and survival. Cancers (Basel) 2011; 3: 510-30. 
  22. Seidel MF, Herguijuela M, Forkert R, Otten U. Nerve growth factor in rheumatic diseases. Semin Arthritis Rheum 2010; 40: 109-26. 
  23. Banks BE, Vernon CA, Warner JA. Nerve growth factor has anti-inflammatory activity in the rat hindpaw oedema test. Neurosci Lett 1984; 47: 41-5. 
  24. Gigante A, Bevilacqua C, Pagnotta A, Manzotti S, Toesca A, Greco F. Expression of NGF, Trka and p75 in human cartilage. Eur J Histochem 2003; 47: 339-44. 
  25. Smeyne RJ, Klein R, Schnapp A, Long LK, Bryant S, Lewin A, et al. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 1994; 368: 246-9. 
  26. Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee. Osteoarthritis Cartilage 2015; 23 Suppl 1: S8-17. 
  27. McNamee KE, Burleigh A, Gompels LL, Feldmann M, Allen SJ, Williams RO, et al. Treatment of murine osteoarthritis with TrkAd5 reveals a pivotal role for nerve growth factor in non-inflammatory joint pain. Pain 2010; 149: 386-92. 
  28. Voga M, Majdic G. Articular cartilage regeneration in veterinary medicine. Adv Exp Med Biol 2022; 1401: 23-55. 
  29. von Loga IS, El-Turabi A, Jostins L, Miotla-Zarebska J, Mackay-Alderson J, Zeltins A, et al. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Ann Rheum Dis 2019; 78: 672-5. 
  30. Aso K, Izumi M, Okanoue Y, Ikeuchi M. Effects of intraarticular injection of anti-nerve growth factor neutralizing antibody on pain in osteoarthritis rat. Int J Pain Relief 2020; 4: 1-5. 
  31. Dakin P, DiMartino SJ, Gao H, Maloney J, Kivitz AJ, Schnitzer TJ, et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: a phase IIb/III double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheumatol 2019; 71: 1824-34. 
  32. Miyagi M, Ishikawa T, Kamoda H, Suzuki M, Inoue G, Sakuma Y, et al. Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice. BMC Musculoskelet Disord 2017; 18: 428. 
  33. Xu L, Nwosu LN, Burston JJ, Millns PJ, Sagar DR, Mapp PI, et al. The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain. Osteoarthritis Cartilage 2016; 24: 1587-95. 
  34. Majuta LA, Guedon JG, Mitchell SAT, Ossipov MH, Mantyh PW. Anti-nerve growth factor therapy increases spontaneous day/night activity in mice with orthopedic surgery-induced pain. Pain 2017; 158: 605-17. 
  35. LaBranche TP, Bendele AM, Omura BC, Gropp KE, Hurst SI, Bagi CM, et al. Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model. Ann Rheum Dis 2017; 76: 295-302. 
  36. Huang H, Shank G, Ma L, Tallents RH, Kyrkanides S. Nerve growth factor induced after temporomandibular joint inflammation decelerates chondrocyte differentiation. Oral Dis 2013; 19: 604-10. 
  37. Mammoto T, Seerattan RA, Paulson KD, Leonard CA, Bray RC, Salo PT. Nerve growth factor improves ligament healing. J Orthop Res 2008; 26: 957-64. 
  38. Pecchi E, Priam S, Gosset M, Pigenet A, Sudre L, Laiguillon MC, et al. Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in oa pain. Osteoarthritis Cartilage 2014; 22: S23. 
  39. Johnson AC, Farmer AD, Ness TJ, Greenwood-Van Meerveld B. Critical evaluation of animal models of visceral pain for therapeutics development: a focus on irritable bowel syndrome. Neurogastroenterol Motil 2020; 32: e13776. 
  40. Lane NE, Corr M. Osteoarthritis in 2016: anti-NGF treatments for pain - two steps forward, one step back? Nat Rev Rheumatol 2017; 13: 76-8. 
  41. Meng F, Li H, Feng H, Long H, Yang Z, Li J, et al. Efficacy and safety of biologic agents for the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Ther Adv Musculoskelet Dis 2022; 14: 1759720X221080377. 
  42. Pallav M, Zaripova L, Tazhibaeva D, Kabdualieva N. POS1126 clinical efficacy and safety of monoclonal antibody against nerve growth factor and fibroblast growth factor-18 therapy of osteoarthritis. Ann Rheum Dis 2022; 81: 892. 
  43. Leite VF, Buehler AM, El Abd O, Benyamin RM, Pimentel DC, Chen J, et al. Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a systematic review and a meta-analysis. Pain Physician 2014; 17: E45-60. 
  44. Markman JD, Bolash RB, McAlindon TE, Kivitz AJ, Pombo-Suarez M, Ohtori S, et al. Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety. Pain 2020; 161: 2068-78. 
  45. Yang S, Huang Y, Ye Z, Li L, Zhang Y. The efficacy of nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: a metaanalysis. Front Pharmacol 2020; 11: 817. 
  46. Katz N, Borenstein DG, Birbara C, Bramson C, Nemeth MA, Smith MD, et al. Efficacy and safety of tanezumab in the treatment of chronic low back pain. Pain 2011; 152: 2248-58. 
  47. Kivitz AJ, Gimbel JS, Bramson C, Nemeth MA, Keller DS, Brown MT, et al. Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain. Pain 2013; 154: 1009-21. 
  48. Reed NR, Reed WR, Syrett M, Richey ML, Frolov A, Little JW. Somatosensory behavioral alterations in a NGF-induced persistent low back pain model. Behav Brain Res 2022; 418: 113617. 
  49. Peach CJ, Tonello R, Gomez K, Calderon-Rivera A, Bruni R, Bansia H, et al. Neuropilin-1 is a coreceptor for NGF and TrkA-evoked pain. bioRxiv 570398 [Preprint]. 2024 [cited 2024 July 3]. Available at: https://doi.org/10.1101/2023.12.06.570398 
  50. Mai L, Huang F, Zhu X, He H, Fan W. Role of nerve growth factor in orofacial pain. J Pain Res 2020; 13: 1875-82. 
  51. Descamps S, Toillon RA, Adriaenssens E, Pawlowski V, Cool SM, Nurcombe V, et al. Nerve growth factor stimulates proliferation and survival of human breast cancer cells through two distinct signaling pathways. J Biol Chem 2001; 276: 17864-70. 
  52. Verbeke S, Meignan S, Lagadec C, Germain E, Hondermarck H, Adriaenssens E, et al. Overexpression of p75(NTR) increases survival of breast cancer cells through p21(waf1). Cell Signal 2010; 22: 1864-73. 
  53. Lin H, Huang H, Yu Y, Chen W, Zhang S, Zhang Y. Nerve growth factor regulates liver cancer cell polarity and motility. Mol Med Rep 2021; 23: 288. 
  54. Buehlmann D, Ielacqua GD, Xandry J, Rudin M. Prospective administration of anti-nerve growth factor treatment effectively suppresses functional connectivity alterations after cancer-induced bone pain in mice. Pain 2019; 160: 151-9. 
  55. Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG, Jonas BM, et al. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain 2005; 115: 128-41. 
  56. Jimenez-Andrade JM, Ghilardi JR, Castaneda-Corral G, Kuskowski MA, Mantyh PW. Preventive or late administration of anti-NGF therapy attenuates tumorinduced nerve sprouting, neuroma formation, and cancer pain. Pain 2011; 152: 2564-74. 
  57. Guedon JG, Longo G, Majuta LA, Thomspon ML, Fealk MN, Mantyh PW. Dissociation between the relief of skeletal pain behaviors and skin hypersensitivity in a model of bone cancer pain. Pain 2016; 157: 1239-47. 
  58. Jensen TS, Baron R, Haanpaa M, Kalso E, Loeser JD, Rice ASC, et al. A new definition of neuropathic pain. Pain 2011; 152: 2204-5. 
  59. Foley KM. Opioids and chronic neuropathic pain. N Engl J Med 2003; 348: 1279-81. 
  60. Cirillo G, Cavaliere C, Bianco MR, De Simone A, Colangelo AM, Sellitti S, et al. Intrathecal NGF administration reduces reactive astrocytosis and changes neurotrophin receptors expression pattern in a rat model of neuropathic pain. Cell Mol Neurobiol 2010; 30: 51-62. 
  61. McArthur JC, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, et al. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291. Neurology 2000; 54: 1080-8. Erratum in: Neurology 2000; 55: 162. 
  62. Schnitzer TJ, Khan A, Bessette L, Davignon I, Brown MT, Pixton G, et al. Onset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: a 16-week dose-titration study. Semin Arthritis Rheum 2020; 50: 387-93. 
  63. Dai WL, Yan B, Bao YN, Fan JF, Liu JH. Suppression of peripheral NGF attenuates neuropathic pain induced by chronic constriction injury through the TAK1-MAPK/NF-κB signaling pathways. Cell Commun Signal 2020; 18: 66. 
  64. Dos Reis RC, Kopruszinski CM, Nones CF, Chichorro JG. Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats. Behav Pharmacol 2016; 27: 528-35. 
  65. Sainoh T, Sakuma Y, Miyagi M, Orita S, Yamauchi K, Inoue G, et al. Efficacy of anti-nerve growth factor therapy for discogenic neck pain in rats. Spine (Phila Pa 1976) 2014; 39: E757-62. 
  66. Jasim H, Ghafouri B, Gerdle B, Hedenberg-Magnusson B, Ernberg M. Altered levels of salivary and plasma pain related markers in temporomandibular disorders. J Headache Pain 2020; 21: 105. 
  67. Alhilou AM, Shimada A, Svensson CI, Svensson P, Ernberg M, Cairns BE, et al. Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants. Sci Rep 2021; 11: 13873. 
  68. Gao Y, Hu Z, Huang Y, Liu W, Ren C. Efficacy and safety of anti-nerve growth factor antibody therapy for hip and knee osteoarthritis: a meta-analysis. Orthop J Sports Med 2022; 10: 23259671221088590. 
  69. Rahmi, Radithia D, Soebadi B, Parmadiati AE, Winias S. Nerve growth factor and S100B: molecular marker of neuroregeneration after injection of freeze-dried platelet rich plasma. J Oral Biol Craniofac Res 2022; 12: 570-4. 
  70. Boscato N, Exposto FG, Costa YM, Svensson P. Effect of standardized training in combination with masseter sensitization on corticomotor excitability in bruxer and control individuals: a proof of concept study. Sci Rep 2022; 12: 17469. 
  71. Ye Y, Dang D, Zhang J, Viet CT, Lam DK, Dolan JC, et al. Nerve growth factor links oral cancer progression, pain, and cachexia. Mol Cancer Ther 2011; 10: 1667-76. 
  72. Xu XJ, Zhang YL, Liu L, Pan L, Yao SK. Increased expression of nerve growth factor correlates with visceral hypersensitivity and impaired gut barrier function in diarrhoea-predominant irritable bowel syndrome: a preliminary explorative study. Aliment Pharmacol Ther 2017; 45: 100-14. 
  73. Coelho A, Oliveira R, Antunes-Lopes T, Cruz CD. Partners in crime: NGF and BDNF in visceral dysfunction. Curr Neuropharmacol 2019; 17: 1021-38. 
  74. Li Q, Winston JH, Sarna SK. Noninflammatory upregulation of nerve growth factor underlies gastric hypersensitivity induced by neonatal colon inflammation. Am J Physiol Regul Integr Comp Physiol 2016; 310: R235-42. 
  75. Barker K. Targeting pro-inflammatory mediators to treat visceral pain [Doctoral dissertation]. Cambridge: University of Cambridge, 2022. 
  76. Chen Y, Cheng J, Zhang Y, Chen JDZ, Seralu FM. Electroacupuncture at ST36 relieves visceral hypersensitivity via the NGF/TrkA/TRPV1 peripheral afferent pathway in a rodent model of post-inflammation rectal hypersensitivity. J Inflamm Res 2021; 14: 325-39. Erratum in: J Inflamm Res 2021; 14: 393. 
  77. Regmi B, Shah MK. Possible implications of animal models for the assessment of visceral pain. Animal Model Exp Med 2020; 3: 215-28. 
  78. Liang D, Ren Y, Huang L, Jin S. A study on the mechanism of electroacupuncture to alleviate visceral pain and NGF expression. Comput Intell Neurosci 2022; 2022: 3755439. 
  79. Jiao Y, Lin Y, Zheng J, Shi L, Zheng Y, Zhang Y, et al. Propionibacterium acnes contributes to low back pain via upregulation of NGF in TLR2-NF-κB/JNK or ROS pathway. Microbes Infect 2022; 24: 104980. 
  80. Rizzo RRN, Ferraro MC, Wewege MA, Cashin AG, Leake HB, O'Hagan ET, et al. Targeting neurotrophic factors for low back pain and sciatica: a systematic review and meta-analysis. Rheumatology (Oxford) 2022; 61: 2243-54. 
  81. Delivanoglou N, Boziki M, Theotokis P, Kesidou E, Touloumi O, Dafi N, et al. Spatio-temporal expression profile of NGF and the two-receptor system, TrkA and p75NTR, in experimental autoimmune encephalomyelitis. J Neuroinflammation 2020; 17: 41. 
  82. Yeh JF, Akinci A, Al Shaker M, Chang MH, Danilov A, Guileen R, et al. Monoclonal antibodies for chronic pain: a practical review of mechanisms and clinical applications. Mol Pain 2017; 13: 1744806917740233. 
  83. Gwak YS, Bae JY, Jang JH, Yoon DM. Attenuation of spinal cord injury-induced hyperalgesia by administration of antibody to nerve growth factor in the rat. Korean J Pain 2003; 16: 7-13. 
  84. El-Hashim AZ, Jaffal SM, Al-Rashidi FT, Luqmani YA, Akhtar S. Nerve growth factor enhances cough via a central mechanism of action. Pharmacol Res 2013; 74: 68-77. 
  85. Minnone G, De Benedetti F, Bracci-Laudiero L. NGF and its receptors in the regulation of inflammatory response. Int J Mol Sci 2017; 18: 1028. 
  86. Brown MT, Murphy FT, Radin DM, Davignon I, Smith MD, West CR. Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial. J Pain 2012; 13: 790-8. 
  87. Bernard NJ. NGF vaccine reduces pain. Nat Rev Rheumatol 2019; 15: 251.