The Disease

Neuropathic pain is caused by damage or disease of the sensory nervous system.   There are two different types of neuropathic pain, pain caused by direct damage to a nerve and pain that occurs from normally non-painful stimuli, called allodynia.  Nerve damage pain may also be divided into peripheral and central, where central involves damage to the brain and/or spinal cord while peripheral involves damage to nerves outside the brain or spinal cord.  This latter division is sometimes confusing because lots of conditions cause damage to and/or affect both peripheral and spinal cord nerves and/or they may involve both neuropathic and nociceptive pain and they may also include some aspects of allodynia. (Note: Nociceptic pain is pain caused by stimulation of pain receptors on nerve and is discussed in detail under Pain: Nocioceptic Pain.)   Examples of central neuropathic pain include: spinal cord injury, multiple sclerosis, stroke, etc.  Peripheral pain examples include:  herpes zoster, toxins, radiation injury, physical trauma, etc.  Combined central and peripheral neuropathic pain examples include: diabetes, chemotherapy-induced peripheral pain, some immune disorders, etc.  (Note: Chemotherapy-induced pain and Cancer pain are discussed in detail under Pain: Cancer Related Pain.) 

Allodynia can be divided into 3 types, 1) mechanical: triggered by touching or stroking the skin, 2) thermal: can be triggered by hot or cold but is associated with normally mild changes in skin temperature, and 3) movement allodynia: triggered by normal movements of joints or muscles.  The latter division is often associated with nociceptive pain with the brain learning that if a certain movement occurs (or continues to occur) pain will result.  An example is a sprained ankle.  The first time the abnormal movement occurs, the movement does not cause pain but the damage to the ligaments simulate the pain receptors on the “normal” peripheral nerves and the person feels “real” pain from the damage (nocioceptic pain).  The next time that same movement starts to occur, the central nervous system senses the movement and the person experiences “pain” even before the pain receptors are stimulated and damage has occurred.  This happens because the body is trying to protect itself from damage before the damage occurs.  Over time, this learned response may cause even normal movements to cause perceived pain even though no damage or disease is affecting the nerves.

Opiates are often used in neuropathic pain but increasing doses are often required over time to maintain some degree of pain control.  The side effects (mental dysfunction, addiction, etc.), workplace drug testing, and lack of effective pain control limit the effectiveness of narcotic pain treatment for neuropathic pain.  Antidepressants, anti-epileptic drugs, electro-stimulation, and other treatments have been used with varying degrees of success, however, side-effects often result in discontinuation of therapy.

In summary, the neuropathic pain is often associated with other types of pain especially in the beginning of the course of the disease process but ultimately nerve damage, disease, or disfunction occurs.  Neuropathic pain is often very difficult to treat with modern medications and successful outcomes are rare.

Research Findings  

Chronic pain causes changes in the endocannabinoid system in the spinal cord that can result in allodynia.1,2  Some of these changes can be reversed by phytocannabinoids and several reviews of cannabinoid use in neuropathic pain have concluded that cannabinoids are useful in decreasing both pain caused by damage to central and peripheral nerves and in patients with allodynia, especially in those who are not responding to usual medical treatment.3-5 Studies in animals have shown that CBD is effective in reducing neuropathic pain but the pain relief is enhanced when combined with low amounts of THC.6,7 THC is also effective in reducing neuropathic pain, but the amounts required prohibit its use because of side effects.7  Savitex (an FDA approved combination of 50% THC and 50% CBD) and a synthetic cannabinoid (Naloxone) produce some pain relief in neuropathic pain patients but their side effects far outweigh their advantages.8,9  Numerous studies in humans with pain that is refractory to modern medicines have shown that cannabinoids are effective in decreasing pain in these patients.10,11 In patients with allodynia, cannabinoids have been effective in not only lowering pain but in improving other life functions including: sleep and perceived quality of their condition.12  In an animal model, diabetic neuropathic pain is prevented and reversed with CBD, probably due to its effect in preventing the release of inflammation cytokines in the spinal cord.13,14    The mechanisms of action of CBD in relieving neuropathic pain seem to be multiple including: decreasing inflammatory cytokines released by damaged neurons, decreasing the repetitive firing of sensory neurons in the spinal cord, stimulating morphine-like receptors in the CNS, changing one’s perception of pain in the brain, etc. (Note: see Pain for more information). 15,16

 

Bottom Line

THC/CBD treatment seems to decrease pain in many types of neuropathic pain but the amount required often results in adverse THC-induced side effects.  CBD and CBD-enriched hemp oil have the potential to decrease many of the mechanisms associated with neuropathic pain, but no studies using CBD-enriched hemp oil (without high doses of THC) in humans have been done yet.  The FDA has not yet approved CBD or CBD-enriched hemp oil for use in humans for pain.  

 

                References

  1. Sagar D, etal. Dynamic changes to the endocannabinoid system in models of chronic pain. Phil Trans R Soc B 2012; 367;3300-11.
  2. Starowicz K, Przewlacka B. Modulation of neuropathic-pain-related behaviour by the spinal endocannabinoid/endovanilloid system. Phil Trans R Soc B 2012; 367:3286-99.
  3. Langford RM, et al. A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis.  J Neurol. 2013 Apr;260(4):984-97
  4. Aviram J, Samuelly-Leichtag G. Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Physician. 2017 Sep;20(6):E755-E796.
  5. Boychuk DG, etal. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015 Winter;29(1):7-14.
  6. Casey SL, etal. Cannabis constituent synergy in a mouse neuropathic pain model. Pain 2017; 158(12):2452-60.
  7. Casey S, Vaughan C. Plant-Based Cannabinoids for the treatment of chronic neuropathic pain. Medicines 2018; 5:67.
  8. Mucke M, etal. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 2018 Mar.
  9. Walitt B, et al. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016 Jul 18;7
  10. Hoggart B, et al. A multicentre, open-label, follow-on study to assess the long-term maintenance of effect, tolerance and safety of THC/CBD oromucosal spray in the management of neuropathic pain J Neurol. 2015 Jan;262(1):27-40.
  11. Kahan M, etal. Prescribing smoked cannabis for chronic noncancer pain. Can Fam Phys 2014; 60:1083-90.
  12. Deshpande A, etal. Efficacy and adverse effects of medical marijuana for the chronic noncancer pain. Can Fam Phys 2015; 61:e372-81.
  13. et al. A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment Eur J Pain. 2014 Aug;18(7):999-1012
  14. Toth C, etal. Cannabinoid-medicated modulation of neuropathic pain and microglial accumulation in a murine type I diabetic peripheral neuropathic pain.  Molecular Pain 2010; 6:16.
  15. Wang D, et al. Activated microglia in the spinal cord underlies diabetic neuropathic pain. Eur J Pharmacol. 2014 Apr 5;728:59-66.
  16. Skaper S, Di Marzo V. Endocannabinoids in nervous system health and disease: the big picture in a nutshell.  Phil Trans R Soc B 2012;367:3193-3200.

 

 

 

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