Opioids in the Treatment of Spinal Cord Injuries
Original Editor - Davis Tucker as part of the Winston-Salem State University Pharmacology Project
Chronic pain has been reported in as much as 80% of spinal cord injury patients. Opioid analgesics represent one of the most effective drugs for treating moderate to severe pain associated with spinal cord injury. Strong-agonist opioids such as morphine remain the most popular drugs used to treat severe pain due to their high affinity for mu-receptors located in the CNS. In the spinal cord, opioids act on specific receptors located in pre- and postsynaptic synapses in the dorsal horn. Presynaptically, opioids decrease the release of specific pain neurotransmitters (i.e. substance P), while in the postsynaptic neuron they decrease excitability. Opioid receptors produce their analgesic effects in the spinal cord by coupling with G-proteins to both alter synaptic transmission at pain pathways and to decrease neuronal excitability via the inhibition of cyclic adenosine monophosphate (cAMP).
Preferred route of administration for strong opioid drugs is oral administration. Durations of strong opioid medications such as morphine last up to 4-5 hours, with peak analgesic effects taking place 60 minutes after oral administration. Approximately 30% of morphine is absorbed by the liver, with the drug’s half-life spanning anywhere between 2-4 hours in adult patients. Alternative modes of opioid administration (i.e. Intramuscular) provide a faster onset of peak analgesic effects for longer durations, which permits longer periods of analgesic effects to suppress pain pathways. Epidural administration is perhaps the most effective form of morphine administration for spinal cord injuries because systemic absorption within the spinal meninges will occur, and longer analgesic effects (up to 24-48 hours) can provide patient comfort.
Adverse Effects of Opioids
Opioid medications can produce a variety of side effects in both the central and peripheral nervous systems. Common side effects of opioid use include drowsiness, nausea, and mood changes. A chief concern for patients who are prescribed opioids is the risk for addiction. Inappropriate use of opioids can limit the analgesic effects by physiological processes such as desensitization or receptor down-regulation. Decreased sensitivity to opioid receptors increases the need for higher opioid doses to achieve analgesic effects. Drugs such as buprenorphine can be substituted for patients suffering from opioid addiction. Buprenorphine’s ability to stimulate mu-opioid receptors while simultaneously blocking kappa receptors helps prevent withdrawal symptoms and affects cellular changes that cause addiction.
Implications for Physical Therapy
Physical therapists must be very mindful when treating spinal cord injury patients who are prescribed opioids. Patient education on the potential side effects of opioids (GI distress, drowsiness, etc.), as well as planning optimal treatment times around patient dosage schedules are important to encourage as much patient participation in treatment as possible. Clinicians should monitor signs of addiction in patients, but must also be aware of instances when opioids do not produce their therapeutic effects. If the patient fails to respond to the drug’s analgesic effects, such as in the case of opioid-induced hyperalgesia, patients might complain of increased pain during their current opioid prescription. Clinicians should contact the patient’s physician when opioid prescriptions fail to produce analgesic effects. To achieve optimal outcomes from physical therapy, it is imperative for spinal cord patients to follow dosage schedules and to report noticeable side effects of opioid use with their care team.
- Sezer,N., Akkuş, S., & Uğurlu, F. G. (2015). Chronic Complications of Spinal Cord Injuries. Retrieved September 5, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303787
- Schumacher et al. Opioid analgesics and antagonists. In: Katzung BG Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology. 12thed. New York: Lange Medical Books/McGraw Hill; 2012:544.
- Dickenson AH, Kieffer B. Opioids: basic mechanisms. In: McMahon SB, Koltzenberg M, eds. Wall and Melzack’s Textbook of Pain. 5thed. New York: Elsevier/Churchill Livingstone; 2005: 427-442.
- Heinke B, Gingl E, Sandkühler J. Multiple targets of m-opioid receptor-mediated presynaptic inhibition at primary afferent Ad- and C-fibers. J Neurosci. 2011;31:1313-1322.
- Wang Q, Traynor JR. Modulation of m-opioid receptor signaling by RGS19 in SH-SY5Y cells. MolPharmacol.2013;83:512-520.
- Ciccone CD. Davis's Drug Guide for Rehabilitation Professionals. Philadelphia: F.A. Davis; 2013.
- Ciccone, C. D. (2016). Pharmacology in rehabilitation (5th ed.). Philadelphia: F.A. Davis Company.
- Ahlbeck K. Opioids: a two-faced Janus. Curr Med Res Opin. 2011;27:439-438.
- Mercadante S. Prospects and challenges in opioid analgesia for pain management. Curr Med Res Opin. 2011;27:1741-1743.
- Ueda H, Ueda M. Mechanisms underlying morphine analgesic tolerance and dependence. Front Biosci. 2009;14:5260-5272.
- Bonhomme J, Shim RS, Gooden R, Tyus D, Rust G. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options. J Natl Med Assoc. 2012;104:342-350.
- Lee M, Silverman SM, Hansen H, et al. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14:145-161.
- Raffa RB, Pergolizzi JV Jr. Multi-mechanistic analgesia for opioid-induced hyperalgesia. Pain Physician. 2011;14:145-161.