From the Guidelines
The nervous system processes pain through a complex pathway that begins when specialized nerve endings called nociceptors detect potentially harmful stimuli, and pain misinterpretation can occur through several mechanisms, including central sensitization, neuroplastic changes, and psychological factors, as supported by recent studies 1.
Mechanisms of Pain Processing
The process of pain transmission involves the activation of nociceptors, which convert the painful stimulus into electrical signals that travel along peripheral nerves to the spinal cord through A-delta and C fibers. In the spinal cord, these signals synapse with second-order neurons that cross to the opposite side and ascend to the brain through the spinothalamic tract. The brain then processes this information in multiple areas, including the thalamus, somatosensory cortex, limbic system, and prefrontal cortex, to create the conscious experience of pain.
Pain Misinterpretation
Pain misinterpretation can occur through several mechanisms, including:
- Central sensitization, which can develop when persistent pain signals cause the nervous system to become hypersensitive, leading to increased pain perception even from non-painful stimuli 1.
- Neuroplastic changes in the brain and spinal cord, which can maintain pain signals even after the original injury has healed 1.
- Psychological factors, such as anxiety, depression, and past trauma, which can amplify pain perception through descending pain pathways 1.
- Conditions like phantom limb pain, which demonstrate how the brain can generate pain sensations without actual tissue damage, as pain memories and neural representations persist despite the absence of the limb 1.
Clinical Implications
Understanding these mechanisms helps explain why pain can persist chronically and why treatments must often address both physical and psychological components. A multidisciplinary approach to pain management, including pharmacological and non-pharmacological interventions, can be effective in reducing pain and improving quality of life 1.
From the FDA Drug Label
Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's anti-nociceptive and antiseizure effects in animals In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing-calcium channel trafficking and/or reducing calcium currents Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord
The nervous system processes pain through complex mechanisms involving the release of pro-nociceptive neurotransmitters in the spinal cord and the modulation of pain transmission by descending noradrenergic and serotonergic pathways. The nervous system can misinterpret pain due to nerve damage or persistent pain, leading to abnormal pain transmission. Pregabalin's anti-nociceptive effects may be mediated by its binding to the alpha2-delta subunit and its interaction with these pathways, although the exact mechanism is not fully understood 2.
- Key points:
- The nervous system processes pain through complex mechanisms
- Nerve damage or persistent pain can lead to abnormal pain transmission
- Pregabalin's anti-nociceptive effects may be mediated by its binding to the alpha2-delta subunit and interaction with descending noradrenergic and serotonergic pathways
- The exact mechanism of pregabalin's action is not fully understood 2
From the Research
Nervous System Processing of Pain
The nervous system processes pain through a complex interplay of messages sent from the periphery to the central nervous system and vice versa, involving specific pathways that carry and modulate these messages 3. The anatomy and physiology of pain involve the transmission and parcellation of noxious stimuli from the peripheral nervous system to the central nervous system, as well as inhibitory and excitatory systems that regulate pain 4.
Pain Pathways and Modulation
Pain pathways play a vital role in carrying messages from the periphery to the central nervous system, and modulating or exacerbating their downstream effects 3. The nervous system can misinterpret pain due to dysfunction in these pathways, leading to chronic pain conditions. The psychobiological mediation of nociception and pain involves cognitive, emotional, and behavioral factors that are central to the pain experience 5.
Factors Influencing Pain Perception
Several factors can influence pain perception, including:
- Cognitive factors, such as attention and expectation 5
- Emotional factors, such as stress and anxiety 5
- Behavioral factors, such as coping mechanisms and lifestyle habits 5
- Neurochemical factors, such as the release of neurotransmitters and hormones 4
Treatment of Pain
The treatment of pain often involves a combination of pharmacological and non-pharmacological approaches. Pharmacological treatments for neuropathic pain include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, pregabalin, and gabapentin as first-line treatments, with lidocaine plasters and capsaicin high concentration patches as second-line treatments for peripheral neuropathic pain 6. For acute pain, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen can provide adequate analgesia, although combination therapy using a small amount of opioid together with a nonopioid pain reliever may be effective in reducing opioid consumption 7.