Turn down the amplification

As seen in the December issue of Retail Pharmacy magazine. 

Of the growing number of Australians who experience chronic pain, around 20 per cent suffer from neuropathic pain.¹ In these individuals, up to 75 per cent report moderate to severe pain despite the use of analgesics.²

While pain is multifaceted and complex, neuroinflammation is often a key feature of neuropathic pain, and the need for effective therapeutic cover is paramount.

Mel Nash, Healthcare Practitioner Education Specialist at Metagenics, says pharmacists can play a key role in helping patients find appropriate complementary pain treatment.

“As highly trained and trusted healthcare professionals, pharmacists are considered to be more readily accessible than other community health providers,” she said.

“Over 60 per cent of pain sufferers surveyed said they would like their pharmacy or pharmacist to offer more solutions when it comes to their pain management.”³

Know your pain

The classification of nociplastic pain as a new pain descriptor was postulated in 2016.⁴

Ms Nash says that when the body’s natural responses to nerve pain and damage fail to resolve, or when the stimuli cannot be removed or adequately treated, there is:

• Increased nociceptor sensitivity.⁵
• Glial cell-mediated inflammation.⁶
• Increased pain neurotransmission.⁷
• Downregulation of opioid receptors.⁸

“Combined, these factors may lead to central sensitisation, defined as an [pain in response to non-painful stimuli] and hyperalgesia [exaggerated pain perception], a hallmark feature in nociplastic pain,⁹ and involves specific changes to the nervous system, particularly at the receptor sites,” she said.¹⁰

“There’s currently no conclusive diagnostic criteria or tests for central sensitisation. However, it’s considered likely to be present in many, if not all chronic pain cases.”

According to Ms Nash, pain researchers point out that nociplastic pain responds differently to therapies than nociceptive pain – that is, pain caused by damage to body tissue.

“There’s decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections,” she said.¹⁰

Breaking the cycle

Pain amplification occurs when neuropathic pain triggers an inflammatory process at the site of nerve injury, through the release of neuropeptides.¹¹ 

This in turn prompts the release of inflammatory mediators by local mast cells to facilitate tissue healing.¹²

However, persistent neuron damage can prolong neuroinflammation and amplify pain signalling, says Ms Nash.

This can “increase nerve excitability and decrease pain tolerance, leading to pain hypersensitivity and the pain cycle continues”.

Strategies that effectively downregulate neuroinflammation and desensitise pain sensory receptors have been identified as effective targets for neuropathic pain^{13, 14, 15, 16} and may assist in the management of chronic pain.¹⁷

Nervalgesic, part of the Ethical Nutrients Clinical range, is promoted as offering a unique combination of synergistic ingredients to address central sensitisation and downregulate pain amplification.

Available exclusively to pharmacists for recommendation to their customers in Australian pharmacies, Nervalgesic combines palmitoylethanolamide (PEA), saffron and thiamine to offer “effective pain relief”, and can be recommended alongside analgesic medications.

“Supported by clinical data, these ingredients help to downregulate both nociceptor sensitivity and glial cell activation that contribute to the chronic pain cycle, providing analgesic, anti-inflammatory and neuroprotective benefits to enhance clinical outcomes in chronic pain sufferers,” Ms Nash said.

PEA at 600mg/day has been successfully used in several human clinical trials for neuralgia and neuropathic pain to decrease symptoms and improve quality of life in conditions such as lumbosciatica^{18, 19, 20}, and back pain^{21, 22} with several studies highlighting 70 per cent improvement in subjective pain scores over three weeks. The PEA used in Nervalgesic (Levagen) is more highly bioavailable than standard PEA and thus able to be offered at convenient doses.²³

Ms Nash says chronic pain can impact the quality of life of many sufferers who are searching for adequate therapeutic cover, often in addition to their current medications or topical treatments.

“Being able to offer an adjunct therapy, such as a combination of PEA, saffron and thiamine, across the dispensary counter could provide improvements and reduction in your customers’ pain scores to help them live a happier, healthier life.”

References 

1. Henderson J, Pollack AJ, Pan Y, Miller GC. ‘Neuropathic and non-neuropathic chronic pain at GP encounters: prevalence, patient characteristics, suffering and pregabalin use’. Aust Fam Physician, 2016 Nov; 45 (11): 783-86.
2. O’Connor AB. ‘Neuropathic pain: quality of life impact, costs and cost-effectiveness of therapy’. PharmacoEconomics, 2009; 27 (2): 95-112. doi: 10.2165/00019053-200927020-00002.
3. Mishriky J, et al. ‘An investigation of the practices of Australian adults experiencing pain and their views of Australian community pharmacy pain management services’. Pharmacy (Basel), 2020 Oct 13; 8 (4): 187. doi: 10.3390/pharmacy8040187;
4. Kosek E, et al. ‘Do we need a third mechanistic descriptor for chronic pain states?’ Pain,2016; 157: 1382–86.
5. Gouin O, et al. ‘TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitisation’. Protein & Cell, 2017 Sep; 8 (9): 644-661. doi: 10.1007/s13238-017-0395-5
6. Ji RR, Berta T, Nedergaard M. ‘Glia and pain: is chronic pain a gliopathy?’ Pain, 2013 Dec; 154 Suppl 1 (1): S10-S28. doi: 10.1016/j.pain.2013.06.022.
7. Souza Monteiro de Araujo D, et al. ‘TRPA1 as a therapeutic target for nociceptive pain’. Expert Opin Ther Targets, 2020 Oct; 24 (10): 997-1008. doi: 10.1080/14728222.2020.1815191
8. Zheng BX, et al. ’Nerve trauma-caused downregulation of opioid receptors in primary afferent neurons: molecular mechanisms and potential managements’. Exp Neurol, 2021 Mar; 337: 113572. doi: 10.1016/expneurol, 2020.113572.
9. Fitzcharles M-A, et al. ‘Nociplastic pain: towards an understanding of prevalent pain conditions’. Lancet, 2021 May; 397 (10289): 2098-2110. doi.org/10.1016/S0140-6736(21)00392-5
10. Curatolo M, Arendt-Nielsen L, Petersen-Felix S. ‘Central hypersensitivity in chronic pain: mechanisms and clinical implications’. Phys Med Rehabil Clin N Am, 2006; 17: 287-302. doi: 10.1016/j.pmr.2005.12.010
11. D’Amico R, et al. ‘ALIAmides update: Palmitoylethanolamide and its formulations on management of peripheral neuropathic pain’. Int J Mol Sci, 2020 Jul 27; 21 (15): 5330. doi: 10.3390/ijms21155330.
12. Héron A, Dubayle D. ‘A focus on mast cells and pain’. J Neuroimmunol, 2013 Nov 15; 264 (1-2): 1-7. doi: 10.1016/j.jneuroim.2013.09.018.
13. Jara-Oseguera A, Simon SA, Rosenbaum T. ‘TRPV1: on the road to pain relief’. Curr Mol Pharmacol, 2008 Nov; 1 (3): 255-69. doi: 10.2174/1874467210801030255
14. Souza Monteiro de Araujo D, et al. ‘TRPA1 as a therapeutic target for nociceptive pain’. Expert Opin Ther Targets, 2020 Oct; 24 (10): 997-1008. doi: 10.1080/14728222.2020.1815191.
15. Moran MM. ‘TRP channels as potential drug targets’. Annu Rev Pharmacol Toxicol, 2018 Jan 6; 58: 309-30. doi: 10.1146/annurev-pharmtox-010617-052832.
16. Moran MM, Szallasi A. ‘Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field’. Br J Pharmacol, 2018 Jun; 175 (12): 2185-2203. doi: 10.1111/bph.14044.
17. O’Connor AB. ‘Neuropathic pain: quality of life impact, costs and cost-effectiveness of therapy’. PharmacoEconomics, 2009; 27 (2): 95-112. doi: 10.2165/00019053-200927020-00002.
18. Guida G, et al. ‘Palmitoylethanolamide (Normast) in chronic neuropathic pain by compressive type lumbosciatalgia: multicentric clinical study’. DOLOR, 2010; 25 (1): 35–42
19. Keppel Hesselink JM, Kopsky DJ. ‘Palmitoylethanolamide, a neutraceutical, in nerve compression syndromes: efficacy and safety in sciatic pain and carpal tunnel syndrome’. J Pain Res, 2015 Oct 23; 8: 729-34. doi: 10.2147/JPR.S93106.
20. Domínguez CM, et al. ‘N-palmitoylethanolamide in the treatment of neuropathic pain associated with lumbosciatica’. Pain Manag, 2012 Mar; 2 (2): 119-24. doi: 10.2217/pmt.12.5
21. Paladini A, et al. ‘Palmitoylethanolamide in the treatment of failed back surgery syndrome’. Pain Res Treat, 2017: 1486010. doi: 10.1155/2017/1486010.
22. Passavanti MB, et al. ‘The beneficial use of ultra micronised palmitoylethanolamide as add-on therapy to tapentadol in the treatment of low back pain: a pilot study comparing prospective and retrospective observational arms’. BMC Anesthesiol, 2017 Dec 19; 17 (1): 171. doi: 10.1186/s12871-017-0461-9.
23. Briskey D. ‘Increased absorption of palmitoylethanolamide using a novel dispersion technology system (LipiSperse)’. J Nutraceuticals Food Sci, 2020 May; 5 (2): 3. doi: 10.36648/nutraceuticals.5.2.3.