Pain can have a devastating effect on the quality of life of patients in palliative medicine. Thus far, majority of research has been centered on
opioid-based
pain management, with a limited empirical evidence for the use of nonopioid medications in
palliative care. However,
opioid and nonopioid medications such as nonsteroidal anti-inflammatory drugs have their limitations in the clinical use due to risk of adverse effects, therefore, there is a need for more research to be directed to finding an alternative approach to
pain management in comfort care setting. The purpose of this article is to discuss a potential new
drug that would adequately alleviate
pain and enhance quality of life without significant risks of adverse effects that would limit its use.
Naltrexone is a reversible competitive antagonist at μ-
opioid and κ-
opioid receptors, which when used at standard doses of 50 to 150 mg was initially intended for use in
opioid and
alcohol use disorders. However, it was discovered that its use in low doses follows alternate pharmacodynamic pathways with various effects. When used in doses of 1 to 5 mg it acts as a glial modulator with a
neuroprotective effect via inhibition of microglial activation. It binds to
Toll-like receptor 4 and acts as an antagonist, therefore inhibiting the downstream cellular signaling pathways that ultimately lead to pro-inflammatory
cytokines, therefore reducing inflammatory response. Its other mode of action involves transient
opioid receptor blockade ensuing from low-dose use which upregulates
opioid signaling resulting in increased levels of endogenous
opioid production, known as
opioid rebound effect. Low dose
naltrexone has gained popularity as an off-label treatment of several
autoimmune diseases including
multiple sclerosis and
inflammatory bowel disease, as well as
chronic pain disorders including
fibromyalgia,
complex regional pain syndrome, and
diabetic neuropathy. Low-dose
naltrexone (LDN) may also have utility in improving
mood disorders and the potential to enhance the quality of life. This article will therefore propose the potential
off-label use of LDN in management of nonmalignant
pain in the palliative medicine setting.