Hyperalgesia is when someone has an increased sensitivity to pain from disruptions in the nerve pathways in the brain, resulting in a more extreme response to pain. Chronic opioid use can lead to what is known as opioid-induced hyperalgesia (OIH), which reduces the pain-relieving effects of opioids and, in turn, intensifies the pain.
Chronic Opioid Use and Opioid-Induced Hyperalgesia
Prescription opioids, including oxycodone (OxyContin), hydrocodone (Vicodin), morphine, and methadone, are widely prescribed by healthcare professionals to treat patients with moderate to severe pain. While the purpose of opioids is to help with pain relief and management, over time, they can start doing more harm than good. Rising opioid abuse in the U.S. continues to fuel the opioid crisis, with over 75% of overdose deaths in 2021 involving opioids.
When someone is taking opioids for an extended period, they can become immune to its effects and more sensitive to pain. This is known as opioid-induced hyperalgesia (OIH) when opioid medications change the way the body handles pain signals in the central nervous system (CNS). Hyperalgesia from opioid use is not the same as developing a tolerance; instead, it is known as hypersensitization. Hypersensitization is when the body tries to fight the pain signals that are being blocked by opioids by activating other pain signals and pathways.
Opioids may activate glial cells in the spinal cord and central nervous system (CNS) and release cytokines, contributing to pain sensitivity. Prolonged exposure to opioid medications can also interfere with the balance of pain modulation, heightening one’s perception of pain. N-methyl-D-aspartate (NMDA) receptors contribute to developing pain tolerance and hyperalgesia and can be activated by certain opioids.
How Opioid Abuse Leads to Hyperalgesia
Opioid-induced hyperalgesia (OIH) is a condition in which someone who abuses opioids experiences an increase in sensitivity to painful stimuli. OIH does the exact opposite of what opioids are supposed to, increasing pain perception rather than providing relief. Some might misinterpret OIH as developing a tolerance to opioids, but they are not the same. Opioid tolerance develops over time when someone becomes immune to the analgesic effects and is typically resolved with a higher dosage. Hyperalgesia is when someone experiences an extreme response to painful stimuli, which exacerbates with a higher opioid dose. Chronic opioid use can not only exacerbate hyperalgesia but can also facilitate the onset of it by activating NMDA receptors and glial cells, as well as disrupting pain pathways.
NMDA Receptor Activation
Chronic opioid use can activate N-methyl-D-aspartate (NMDA) receptors, which are glutamate receptors, the primary excitatory neurotransmitter in the brain. Since NMDA receptors play a role in central sensitization and pain sensation, activating these receptors can intensify pain sensitivity and contribute to the development of opioid-induced hyperalgesia (OIH).
Central Sensitization
Central sensitization occurs when the central nervous system (CNS) experiences changes that make it more sensitive to pain and other sensory stimuli. Opioids can induce these changes, amplifying the body’s response to pain signals and contributing to hyperalgesia.
Glial Cell Activation
The activation of glial cells in the brain and spinal cord is a critical mechanism for underlying chronic pain. While opioids are common prescription analgesics for managing chronic pain, they can activate glial cells by directly impacting opioid receptors. Glial cells release pro-inflammatory cytokines and chemokines, inducing an inflammatory response that intensifies pain sensitivity. Opioid-induced glial activation enhances opioid tolerance and dependence, ultimately fighting the analgesic effects of opioids.
Disruption of Descending Pain Pathways
Opioids mediate both ascending and descending pain pathways that are responsible for modulating pain signals in the spinal cord. Chronic opioid use can disrupt these pain pathways, reducing their inhibitory effect and resulting in an enhanced perception of pain.
Alterations in Pain Modulation
The body’s natural ability to modulate pain revolves around the balance between excitatory (glutamate and glycine) and inhibitory mechanisms. When opioids are abused, this natural balance is disrupted and results in reduced efficacy of the body’s natural pain inhibitions. Interfering with the body’s pain-inhibiting patterns can amplify one’s pain perception and ultimately reduce one’s tolerance.
Managing and Treating Opioid-Induced Hyperalgesia from Opioid Abuse
Treating opioid-induced hyperalgesia (OIH) requires a comprehensive approach that addresses the medical aspects of hyperalgesia as well as the underlying issue of opioid abuse. Addressing opioid abuse in patients with increased pain sensitivity often requires tapering off opioids, as they are contributing to hyperalgesia. Some cases of opioid-induced hyperalgesia (OIH) might require a medical drug detox to manage opioid withdrawal symptoms effectively.
Medical detox provides patients struggling with opioid abuse and addiction the necessary treatment and tools for an effective and safe withdrawal process. Medication-assisted detox for opioid abuse and hyperalgesia might incorporate non-opioid pain medications that can help patients manage their pain without exacerbating their hyperalgesia or addiction.
Cognitive behavioral therapy (CBT) and psychotherapy can help individuals with OIH adopt healthy coping mechanisms for their pain and stress. Lifestyle modifications such as regular physical activity, a healthy diet, and practicing stress management techniques can improve physical and mental health and overall well-being. Holistic therapies such as massage therapy or acupuncture can be helpful when withdrawing from opioids and improving pain tolerance.
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References:
- Cleveland Clinic, 2022. Hyperalgesia.
- Centers for Disease Control and Prevention, 2023. Understanding the Opioid Overdose Epidemic.
- Harvard Health Publishing, 2019. More opioids, more pain: Fueling the fire.
- American Society of Anesthesiologists, 2006. Opioid-induced Hyperalgesia: A Qualitative Systematic Review.
- American Society of Anesthesiologists, 2016. Differential Opioid Tolerance and Opioid-induced Hyperalgesia: A Clinic Reality.
- National Library of Medicine, 2022. Physiology, NMDA Receptor.
- Cleveland Clinic Journal of Medicine, 2023. Central sensitization, chronic pain, and other symptoms: Better understanding, better management.
- National Library of Medicine, 2013. Glia and pain: Is chronic pain a gliopathy?
- National Library of Medicine, 2009. The “Toll” of Opioid-Induced Glial Activation: Improving the Clinical Efficacy of Opioids by Targeting Glia.
- National Library of Medicine, 2023. Biochemistry, Endogenous Opioids.