Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 Keywords entry + 978 word(s) 978 2020-09-08 10:45:12 |
2 Format correct + 55 word(s) 1033 2020-09-17 05:54:24 | |
3 Format correct -130 word(s) 903 2020-10-27 08:42:12 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Hossain, M.Z.; Ando, H.; Unno, S.; Kitagawa, J. Endocannabinoid for Neuropathic Orofacial Pain. Encyclopedia. Available online: https://encyclopedia.pub/entry/1991 (accessed on 27 July 2024).
Hossain MZ, Ando H, Unno S, Kitagawa J. Endocannabinoid for Neuropathic Orofacial Pain. Encyclopedia. Available at: https://encyclopedia.pub/entry/1991. Accessed July 27, 2024.
Hossain, Mohammad Zakir, Hiroshi Ando, Shumpei Unno, Junichi Kitagawa. "Endocannabinoid for Neuropathic Orofacial Pain" Encyclopedia, https://encyclopedia.pub/entry/1991 (accessed July 27, 2024).
Hossain, M.Z., Ando, H., Unno, S., & Kitagawa, J. (2020, September 11). Endocannabinoid for Neuropathic Orofacial Pain. In Encyclopedia. https://encyclopedia.pub/entry/1991
Hossain, Mohammad Zakir, et al. "Endocannabinoid for Neuropathic Orofacial Pain." Encyclopedia. Web. 11 September, 2020.
Endocannabinoid for Neuropathic Orofacial Pain
Edit

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system [1][2]. Neuropathic pain in the orofacial regions (e.g., head, neck, face, oral, or perioral regions) can be termed as neuropathic orofacial pain (NOP) and may arise from nerve compression or injury to peripheral nerves during dental operative procedures, such as tooth extraction, root canal treatment, and dental implant surgery (e.g., trigeminal neuralgia, post-traumatic trigeminal neuropathy) as well as from systemic diseases (e.g., diabetic neuropathy), viral infections (e.g., trigeminal post-herpetic neuralgia) and neurovascular diseases (e.g., tension type headache, chronic/episodic migraine) [3][4][5][6][7]. NOP may be characterized by spontaneous pain (ongoing or episodic), pain resulting from stimuli that would not normally provoke pain (allodynia) and exaggerated pain responses to noxious stimuli (hyperalgesia) [3][4][5][6].

neuropathic orofacial pain CB2-selective agonists peripherally restricted CB1 agonists endocannabinoid-degrading enzyme inhibitors

1. Introduction

Neuropathic pain is a health problem that has negative impacts on both the individual quality of life and the community [8]. It is associated with significant societal costs resulting from greater healthcare utilization, disability, and loss of productivity [9][10]. Patients with poorly controlled neuropathic pain have significantly poorer health status and increased symptoms of anxiety and depression [9][10]. The mechanisms of neuropathic pain are complex, rendering it a challenge for clinicians to treat effectively [11][12][13]. Tricyclic antidepressants (e.g., nortriptyline, desipramine), serotonin–noradrenaline reuptake inhibitors (e.g., duloxetine), and anticonvulsants (e.g., gabapentin, pregabalin) are currently used as first-line treatments for neuropathic pain; however, many patients report incomplete relief of pain as well as adverse effects of these drugs such as cardiotoxicity, dry mouth, orthostatic hypotension, constipation, and dizziness [11][12]. Topical lidocaine (which only acts locally) and opioids (e.g., morphine) are considered as second- and third-line drugs for treatment of neuropathic pain. Opioids have adverse effects including sedation, constipation, physical dependence, respiratory depression tolerance, and addiction [11][12][14], and they have a high degree of abuse potential [15]. The management of neuropathic pain with these contemporary pharmacotherapies exhibits a high failure rate [11][12][13]. These treatment failures may occur because of lack of analgesic efficacy, intolerance, contraindications to various classes of medications and the presence of side effects [9][10][11][12][13]. Therefore, a major priority in pain-related research is to identify new therapeutic strategies for treating neuropathic pain. In recent decades, cannabinoid- and endocannabinoid-based therapeutic strategies for neuropathic pain treatment have gained popularity [16][17][18][19][20][21].

2. The Effectiveness of Cannabinoids in Chronic Pain Treatment

Various studies have reported that natural and synthetic cannabinoids are effective in the attenuation of acute and chronic pain including neuropathic pain [21][22][23][24][25]. However, the major drawback of using cannabinoids for pain relief is their side effects (cannabimimetic side effects), including sedation, catalepsy (the body becomes stiff), hypothermia, addiction, hypo-locomotion or motor impairment, cognitive impairment and psychological problems [26][27][28]. These cannabimimetic side effects are thought to arise mainly because of global activation of the widespread distribution of CB1 receptors in the brain [26][27][28][29].

To overcome this problem, several alternative strategies have been developed. One strategy is to target CB1 receptors localized in the peripheral tissues [30][31][32][33]. CB1 agonists with limited or no ability to pass the blood–brain barrier have been developed for this purpose and tested in preclinical animal models [32][33]. Another strategy is to selectively target CB2 receptors because they are predominantly expressed outside of the brain. Studies have reported that CB2 receptor agonists attenuated inflammatory and neuropathic pain [34][35]. Another promising alternative strategy for achieving analgesia is to target endocannabinoids [17][18][36][37][38]. In certain disorders, including neuropathic and inflammatory pain, convincing evidence exists regarding increases in endocannabinoids in certain body regions [17][18][19][36][37]. Exaggerated neuronal activity developed under neuropathic pain conditions may increase the synthesis of endocannabinoids at certain locations of the pain pathway [19][39]. This increase in endocannabinoids may be caused by the body’s autoprotective/defense mechanism; however, the rapid cellular uptake and subsequent degradation of endocannabinoids tends to limit the level of analgesia achieved by endocannabinoids [19][30][37][38]. Reducing the degradation of endocannabinoids by inhibiting their degrading enzymes can elevate their levels at sites where their actions are pertinent and produce analgesia [19][30][37][38]. This strategy of increasing endocannabinoids has the benefit of activation of cannabinoid receptors at sites of pain pathways with high endocannabinoid turnover, rather than global activation of CB1 receptors, which can result in side effects [19][30][37][38].

Analgesic effects of various natural and synthetic cannabinoids for neuropathic pain have widely described and reviewed [16][18][21][22][23]. The presence of cannabimimetic side effects is one of the drawbacks of non-selective cannabinoids due to the widespread distribution of the CB1 receptors in the brain [17][18]. Alternative strategies have developed to overcome this problem by using peripherally acting CB1 receptor agonists, selective CB2 receptor agonists, and endocannabinoid degrading enzyme inhibitors [17][18][19]. These strategies are also applicable to NOP.

3. Conclusions

A large number of preclinical studies have provided evidence that targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoid degrading enzymes is a potentially effective strategy to attenuate neuropathic pain symptoms with limited side effects. In particular, enhancing the action of endocannabinoids at the sites of the pain pathway using endocannabinoid degradative enzyme inhibitors is an attractive strategy for the treatment of neuropathic pain. The combination of endocannabinoid degradative enzyme inhibitors with conventional analgesics that have been used for the treatment of neuropathic pain (e.g., opioids) is also a promising strategy to produce synergistic anti-nociceptive effects and to reduce side effects. Studies examining neuropathic pain in the orofacial regions are scarce; therefore, more basic and clinical studies involving NOP are necessary to understand the efficacy and safety of these alternative strategies for neuropathic pain treatment.

References

  1. Murnion, B.P. Neuropathic pain: Current definition and review of drug treatment. Aust. Prescr. 2018, 41, 60–63. [Google Scholar] [CrossRef]
  2. Merskey, H. Part III Pain Terms, A Current List with Definitions and Notes on usage. In Classification Chronic Pain-Descriptions Chronic Pain Syndromes and Definitions of Pain Terms; IASP Press: Seattle, WA, USA, 1994; pp. 207–214. [Google Scholar]
  3. Benoliel, R.; Sharav, Y. Chronic orofacial pain. Curr. Pain Headache Rep. 2010, 14, 33–40. [Google Scholar] [CrossRef] [PubMed]
  4. Sessle, B.J. Acute and chronic craniofacial pain: Brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit. Rev. Oral Biol. Med. 2000, 11, 57–91. [Google Scholar] [CrossRef] [PubMed]
  5. Maarbjerg, S.; Di Stefano, G.; Bendtsen, L.; Cruccu, G. Trigeminal neuralgia—Diagnosis and treatment. Cephalalgia 2017, 37, 648–657. [Google Scholar] [CrossRef] [PubMed]
  6. Zakrzewska, J.M. Differential diagnosis of facial pain and guidelines for management. Br. J. Anaesth. 2013, 111, 95–104. [Google Scholar] [CrossRef] [PubMed]
  7. Macfarlane, T.V.; Blinkhorn, A.S.; Davies, R.M.; Ryan, P.; Worthington, H.V.; Macfarlane, G.J. Orofacial pain: Just another chronic pain? Results from a population-based survey. Pain 2002, 99, 453–458. [Google Scholar] [CrossRef]
  8. Dueñas, M.; Ojeda, B.; Salazar, A.; Mico, J.A.; Failde, I. A review of chronic pain impact on patients, their social environment and the health care system. J. Pain Res. 2016, 9, 457–467.
  9. McDermott, A.M.; Toelle, T.R.; Rowbotham, D.J.; Schaefer, C.P.; Dukes, E.M. The burden of neuropathic pain: Results from a cross-sectional survey. Eur. J. Pain 2006, 10, 127. [Google Scholar] [CrossRef]
  10. Schaefer, C.; Mann, R.; Sadosky, A.; Daniel, S.; Parsons, B.; Nieshoff, E.; Tuchman, M.; Nalamachu, S.; Anschel, A.; Stacey, B.R. Burden of illness associated with peripheral and central neuropathic pain among adults seeking treatment in the united states: A patient-centered evaluation. Pain Med. 2014, 15, 2105–2119. [Google Scholar] [CrossRef]
  11. Finnerup, N.B.; Attal, N.; Haroutounian, S.; McNicol, E.; Baron, R.; Dworkin, R.H.; Gilron, I.; Haanpää, M.; Hansson, P.; Jensen, T.S.; et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol. 2015, 14, 162–173. [Google Scholar] [CrossRef]
  12. Fornasari, D. Pharmacotherapy for Neuropathic Pain: A Review. Pain Ther. 2017, 6, 25–33. [Google Scholar] [CrossRef] [PubMed]
  13. Torrance, N.; Ferguson, J.A.; Afolabi, E.; Bennett, M.I.; Serpell, M.G.; Dunn, K.M.; Smith, B.H. Neuropathic pain in the community: More under-treated than refractory? Pain 2013, 154, 690–699. [Google Scholar] [CrossRef]
  14. Guirguis-Blake, J.; Kelly, C. Are opioids effective in the treatment of neuropathic pain? Am. Fam. Physician 2007, 75, 999–1001. [Google Scholar]
  15. Thomas, D.A.; Frascella, J.; Hall, T.; Smith, W.; Compton, W.; Koroshetz, W.; Briggs, J.; Grady, P.; Somerman, M.; Volkow, N. Reflections on the role of opioids in the treatment of chronic pain: A shared solution for prescription opioid abuse and pain. J. Intern. Med. 2015, 278, 92–94. [Google Scholar] [CrossRef]
  16. Russo, E.B. Cannabinoids in the management of difficult to treat pain. Ther. Clin. Risk Manag. 2008, 4, 245–259. [Google Scholar] [CrossRef]
  17. Lau, B.K.; Vaughan, C.W. Targeting the endogenous cannabinoid system to treat neuropathic pain. Front. Pharmacol. 2014, 5, 28. [Google Scholar] [CrossRef]
  18. Donvito, G.; Nass, S.R.; Wilkerson, J.L.; Curry, Z.A.; Schurman, L.D.; Kinsey, S.G.; Lichtman, A.H. The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain. Neuropsychopharmacology 2018, 43, 52–79. [Google Scholar] [CrossRef]
  19. Jhaveri, M.D.; Richardson, D.; Chapman, V. Endocannabinoid metabolism and uptake: Novel targets for neuropathic and inflammatory pain. Br. J. Pharmacol. 2007, 152, 624–632. [Google Scholar] [CrossRef]
  20. Jensen, B.; Chen, J.; Furnish, T.; Wallace, M. Medical Marijuana and Chronic Pain: A Review of Basic Science and Clinical Evidence. Curr. Pain Headache Rep. 2015, 19. [Google Scholar] [CrossRef] [PubMed]
  21. Rahn, E.J.; Hohmann, A.G. Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside. Neurotherapeutics 2009, 6, 713–737. [Google Scholar] [CrossRef] [PubMed]
  22. Hill, K.P.; Palastro, M.D.; Johnson, B.; Ditre, J.W. Cannabis and Pain: A Clinical Review. Cannabis Cannabinoid Res. 2017, 2, 96–104. [Google Scholar] [CrossRef] [PubMed]
  23. Jagerovic, N.; Hernandez-Folgado, L.; Goya, P.; Jagerovic, N.; Hernandez-Folgado, L.; Martin, M.I. Cannabinoids and Neuropathic Pain. Mini Rev. Med. Chem. 2003, 3, 159–165. [Google Scholar]
  24. Lynch, M.E.; Campbell, F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br. J. Clin. Pharmacol. 2011, 72, 735–744. [Google Scholar] [CrossRef] [PubMed]
  25. Pertwee, R.G. Cannabinoid receptors and pain. Prog. Neurobiol. 2001, 63, 569–611. [Google Scholar] [CrossRef]
  26. Volkow, N.D.; Baler, R.D.; Compton, W.M.; Weiss, S.R.B. Adverse health effects of marijuana use. N. Engl. J. Med. 2014, 370, 2219–2227. [Google Scholar] [CrossRef]
  27. Thomas, H. A community survey of adverse effects of cannabis use. Drug Alcohol Depend. 1996, 42, 201–207. [Google Scholar] [CrossRef]
  28. Kalant, H. Adverse effects of cannabis on health: An update of the literature since 1996. Prog. Neuro Psychopharmacol. Biol. Psychiatry 2004, 28, 849–863. [Google Scholar] [CrossRef]
  29. Moreira, F.A.; Grieb, M.; Lutz, B. Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: Focus on anxiety and depression. Best Pract. Res. Clin. Endocrinol. Metab. 2009, 23, 133–144. [Google Scholar] [CrossRef]
  30. Spigelman, I. Therapeutic Targeting of Peripheral Cannabinoid Receptors in Inflammatory and Neuropathic Pain States. In Translational Pain Research: From Mouse to Man; CRC Press: Boca Raton, FL, USA, 2010; pp. 99–138. ISBN 9781439812105. [Google Scholar]
  31. Kunos, G.; Osei-Hyiaman, D.; Bátkai, S.; Sharkey, K.A.; Makriyannis, A. Should peripheral CB1 cannabinoid receptors be selectively targeted for therapeutic gain? Trends Pharmacol. Sci. 2009, 30, 1–7. [Google Scholar] [CrossRef]
  32. Banister, S.D.; Krishna Kumar, K.; Kumar, V.; Kobilka, B.K.; Malhotra, S.V. Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain. Medchemcomm 2019, 10, 647–659. [Google Scholar] [CrossRef]
  33. Seltzman, H.H.; Shiner, C.; Hirt, E.E.; Gilliam, A.F.; Thomas, B.F.; Maitra, R.; Snyder, R.; Black, S.L.; Patel, P.R.; Mulpuri, Y.; et al. Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain. J. Med. Chem. 2016, 59, 7525–7543. [Google Scholar] [CrossRef] [PubMed]
  34. Whiteside, G.; Lee, G.; Valenzano, K. The Role of the Cannabinoid CB2 Receptor in Pain Transmission and Therapeutic Potential of Small Molecule CB2 Receptor Agonists. Curr. Med. Chem. 2007, 14, 917–936. [Google Scholar] [CrossRef] [PubMed]
  35. Guindon, J.; Hohmann, A.G. Cannabinoid CB 2 receptors: A therapeutic target for the treatment of inflammatory and neuropathic pain. Br. J. Pharmacol. 2008, 153, 319–334. [Google Scholar] [CrossRef] [PubMed]
  36. Guindon, J.; Hohmann, A. The Endocannabinoid System and Pain. CNS Neurol. Disord. Drug Targets 2012, 8, 403–421. [Google Scholar] [CrossRef] [PubMed]
  37. Woodhams, S.G.; Sagar, D.R.; Burston, J.J.; Chapman, V. The role of the endocannabinoid system in pain. Handb. Exp. Pharmacol. 2015, 227, 119–143. [Google Scholar]
  38. Pertwee, R.G. Targeting the endocannabinoid system with cannabinoid receptor agonists: Pharmacological strategies and therapeutic possibilities. Philos. Trans. R. Soc. B Biol. Sci. 2012, 367, 3353–3363. [Google Scholar] [CrossRef]
  39. Alger, B.E.; Kim, J. Supply and demand for endocannabinoids. Trends Neurosci. 2011, 34, 304–315. [Google Scholar] [CrossRef]
More
Information
Subjects: Others
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , ,
View Times: 403
Revisions: 3 times (View History)
Update Date: 27 Oct 2020
1000/1000
Video Production Service