Chronic pain affects millions of individuals worldwide every year. According to pain Australia, 3.24 million Australians were living with chronic pain in 2018; a figure projected to rise to 5.23 million by 20501. Chronic pain is defined as pain that lasts beyond normal healing time after injury or illness, generally 3 to 6 months, is ongoing and experienced on most days of the week2. The four main categories of pain are neuropathic, musculoskeletal, mechanical, and inflammatory3. Chronic pain can result from injury, surgery, musculoskeletal conditions such as arthritis and osteoporosis, or other medical conditions such as cancer, endometriosis, or migraines. In some cases, there may be no apparent physical cause2, 4.
Most chronic pain patients present with more than one type of pain, and a significant percentage (67%) suffer from a major depressive and generalised anxiety disorder, sleep disturbance and fatigue. Chronic pain can significantly affect a person’s quality of life, use of health care, and their ability to work, study, exercise and socialise3. Patients with chronic pain are also at an increased risk of suicide3. Of the chronic pain patients who commit suicide, approximately 16% die of opioid overdose5.
The mechanisms behind chronic pain
Chronic pain is classified as either nociceptive or neuropathic. Nociceptive pain is the most common type of pain, is usually short-lived and develops in response to a specific situation. Nociceptive pain occurs when a harmful stimulus (e.g. extreme heat or cold, pressure, injury, pinching, or chemicals released during tissue inflammation) activates pain receptors called nociceptors. It normally subsides once the harmful stimulus disappears or heals. However, prolonged or intense exposure to these stimuli, boosts the responsiveness of nociceptive nerve fibres in a process called central sensitisation6. The process increases nerve signal firing and neurotransmitter release in the spinal cord, where sensory information is processed. Central sensitisation generates an abnormally exaggerated response to painful stimuli (hyperalgesia) as well as to normally nonpainful stimuli (allodynia), in conjunction with impaired pain inhibition. Specifically, the transient receptor potential cation channel (TRPV1) has been implicated in allodynia7. Clinical findings suggest that over time, pain hypersensitivity produces structural changes in the brain, which are reversible with pain relief8.
On the other hand, neuropathic pain is not triggered by an external harmful stimulus. Instead, a peripheral nerve lesion induces activity in nerve fibres. Immune cells react at the lesion site in the spinal cord and promote the release of chemicals that modulate the activity of neurons in the vicinity9. One of these mediators, brain-derived neurotrophic factor (BDNF), reduces the inhibitory effect of g-aminobutyric acid (GABA) and glycine. This nerve inhibition further enhances the abnormal input from the lesioned nerve. As in nociceptive pain, central sensitisation occurs and produces a profound imbalance between nerve inhibition and excitation8.
The longer either nociceptive or neuropathic pain remains untreated, the greater the risk of the body becoming sensitised to pain, and the pain becoming chronic. Therefore, timely and effective treatment of acute pain is essential to prevent transition to chronic pain4.
Standard therapies for chronic pain
Because changes occur at all levels of the pain pathway, successful treatment may require a combination of therapies with different mechanisms of action. Thus, best practice does not support long term use of medication for chronic pain management, but a multidisciplinary approach. Multidisciplinary pain management combines various medical, physical, and psychological therapies and has been shown to be the most effective way to improve function and mood and reduce disability.
According to a report by Pain Australia10, after the introduction of multidisciplinary pain treatment, there was a 35% reduction in the use of all health services, and a significant proportion of patients reported improvements in depression (57%) and anxiety (41%). Almost half of chronic pain patients were able to reduce their opioid medication by at least 50%. Multidisciplinary pain treatment may involve the use of drugs (pharmacological) together with non-pharmacological therapies.
The list includes heat and cold therapy, cognitive behavioural therapy, relaxation therapy, biofeedback, group counselling, ultrasound stimulation, acupuncture, aerobic exercise, chiropractic therapy, physical therapy, sleep clinics, osteopathic manipulative medicine, and occupational therapy. Interventional techniques include spinal cord stimulation, epidural steroid injections, radiofrequency nerve ablations, botulinum toxin injections, nerve blocks, trigger point injections, and intrathecal pain pumps3.
Different types of chronic pain will require different treatments, but the general options include nonopioid analgesics such as nonsteroidal anti-inflammatories (NSAIDs), paracetamol, and aspirin. Additionally, medications such as tramadol, opioids, antiepileptic drugs (gabapentin or pregabalin), and topical lidocaine or capsaicin creams have been shown to be effective. Furthermore, antidepressants such as tricyclic antidepressants and serotonin–norepinephrine reuptake inhibitors (SNRIs), topical analgesics, muscle relaxers, N-methyl-d-aspartate (NMDA) receptor antagonists, and alpha 2 adrenergic agonists are also possible pharmacological therapies3.
Opioids are considered a second-line treatment option reserved for patients with severe persistent chronic pain or neuropathic cancer pain. Although there have been conflicting results on the use of opioids in neuropathic pain, they continue to be prescribed on a short-term and intermediate basis. Side effects of opioids are significant and frequent and may include opioid-induced hyperalgesia, constipation, dependence, and sedation. For chronic musculoskeletal pain, they have not been shown to be more effective than nonopioid analgesics3.
There are a number of pain programs available in Australia. For a list of what is available in each state, visit: https://www.painaustralia.org.au/getting-help/pain-programs/programs.
New and potential therapies for chronic pain
Available evidence suggests that efficacious complementary therapies may contribute to the alleviation of chronic pain11. Some of these include acupuncture, complementary medicines, dietary changes, the Feldenkrais Method, hydrotherapy, low-level laser therapy, and medicinal cannabis.
Acupuncture. Recently, there has been growing interest in the use of acupuncture for various pain conditions. Multiple studies have shown its effectiveness in the treatment of back pain, either acute or chronic, knee pain secondary to osteoarthritis, myofascial pain, and headaches . However, it must be noted that there is a significant placebo effect12. The latest review of clinical studies found that migraine and fibromyalgia are two conditions with the most favourable outcomes after acupuncture13.
The Feldenkrais Method (FM). The aim of FM is to improve efficiency of body movement and increased consciousness of how it works. A recent review of seven studies, found that FM improved balance in ageing populations. Although risk of bias was high, the individual studies reported significant positive effects for reduced perceived effort and increased comfort, body image perception, and dexterity14.
Low-level laser therapy (LLLT). This technique uses LED light to produce chemical changes in nerve cells, inhibit pain signaling and promote tissue healing by blocking pain nerves and reducing inflammation, leading to a reduction in central sensitisation and improved circulation15. In combination with other therapies, it has been found to have short-term moderate efficacy in chronic low back and neck pain16.
Medicinal cannabis. A large percentage of the opioid epidemic stems from individuals (90%) suffering from chronic pain17. This has led the medical community to seek safer alternatives such as medicinal cannabis. The endocannabinoid system (ECS) is involved in the regulation of pain sensation and regulates actions at all stages of pain processing pathways18. The ECS is comprised of cannabinoid receptors and endocannabinoids – cannabinoids that are naturally produced in the body and which have analgesic effects. The presence of both of these components has been found in pain circuits from peripheral sensory nerve endings up to the brain19. The cannabinoid 1 (CB1) receptor is involved in the attenuation of synaptic transmission19 and in controlling the release of neurotransmitters such as dopamine, noradrenaline, glutamate, GABA, serotonin and acetylcholine20, 21. The activation of CB1 receptors in the brain modulates nociceptive thresholds and regulates the balance between excitatory and inhibitory neurotransmitters21, 22. The CB1 receptor is also present in cells of the immune system and when activated produces anti-inflammatory effects23. In addition, cannabinoid 2 (CB2) receptors are expressed in several types of inflammatory cells, and their activation generates an antinociceptive response in situations of inflammation and neuropathic pain by suppressing the release of inflammatory mediators by cells located adjacent to nociceptive nerve terminals24, 25. CB2 also indirectly stimulates opioid receptors located in primary neuron pathways26. Evidence suggests that analgesic effects may be also due to the modulation of TRPV1, NMDAR, α-1-adrenoreceptors, serotonin, and several other receptors27, 28.
Cannabidiol (CBD), the major non-psychoactive plant cannabinoid, has been shown to block low-voltage-activated (T-type) calcium channels and stimulate the glycine receptor29-31. The action of CBD via these pathways may be responsible for the suppression of neuronal excitability and pain perception32-34. In addition, CBD and THC (the major psychoactive plant cannabinoid) have been shown to inhibit inflammatory cyclooxygenase 2 (Cox-2), and the production of arachidonic acid metabolites and prostaglandins21, 35-37.
In an exhaustive review, the US National Academies of Science and Medicine has confirmed the efficacy of cannabis for chronic pain in adults17. The European Pain Federation has also indicated that cannabis-based medicines may be appropriate for chronic pain38. In Australia, the Therapeutic Goods Administration (TGA) lists chronic pain as one of the indications for the prescription of medicinal cannabis39.
When given access to cannabis medicines, individuals currently using opioids for chronic pain decrease their use of opioids by 40–60% and report that they prefer cannabis to opioids40-43. In clinical studies, patients have reported fewer side effects with cannabis than with their opioid medications, a reduction in pain, and a better quality of life with cannabis use, compared to opioids43-49.
Overall, it is important to remember that the efficacy and duration of any one therapy will vary according to the type and severity of pain, and on individual patient response, and that they may need to be used in combination, or as an adjunct to standard multidisciplinary therapy.
- Pain in Australia: Pain Australia; 2021 [Available from: https://www.painaustralia.org.au/static/uploads/files/pain-in-australia-20-11-19-at-2-23pm-wffqorflohoq.pdf].
- Chronic Pain in Australia.: Australian Institute of Health and Welfare. Australian Government.; 2020 [Available from: https://www.aihw.gov.au/getmedia/10434b6f-2147-46ab-b654-a90f05592d35/aihw-phe-267.pdf.aspx?inline=true].
- Dydyk AM, Yarrarapu SNS, Conermann T. Chronic Pain.StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC.; 2020.
- What is chronic pain? : Pain Australia.; 2021 [Available from: https://www.painaustralia.org.au/about-pain/what-is-chronic-pain].
- Petrosky E, Harpaz R, Fowler KA, Bohm MK, Helmick CG, Yuan K, et al. Chronic Pain Among Suicide Decedents, 2003 to 2014: Findings From the National Violent Death Reporting System. Ann Intern Med. 2018;169(7):448-55.
- Petho G, Reeh PW. Sensory and signaling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors. Physiol Rev. 2012;92(4):1699-775.
- Courtney CA, Fernández-de-Las-Peñas C, Bond S. Mechanisms of chronic pain – key considerations for appropriate physical therapy management. The Journal of manual & manipulative therapy. 2017;25(3):118-27.
- Scholz J. Mechanisms of chronic pain. Molecular Pain. 2014;10(Suppl 1):O15-O.
- Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10(11):1361-8.
- Electronic Persistent Pain Outcomes Collaboration. : Pain Australia; 2021 [Available from:https://www.painaustralia.org.au/static/uploads/files/electronic-persistent-pain-outcomes-collaboration-14-11-2019-wffowrramcja.jpg].
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- Patel M, Urits I, Kaye AD, Viswanath O. The role of acupuncture in the treatment of chronic pain. Best Pract Res Clin Anaesthesiol. 2020;34(3):603-16.
- Hillier S, Worley A. The effectiveness of the feldenkrais method: a systematic review of the evidence. Evid Based Complement Alternat Med. 2015;2015:752160.
- Cotler HB, Chow RT, Hamblin MR, Carroll J. The Use of Low Level Laser Therapy (LLLT) For Musculoskeletal Pain. MOJ orthopedics & rheumatology. 2015;2(5):00068.
- Skelly AC, Chou R, Dettori JR, Turner JA, Friedly JL, Rundell SD, et al. AHRQ Comparative Effectiveness Reviews.Noninvasive Nonpharmacological Treatment for Chronic Pain: A Systematic Review Update. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020.
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