Pain Modulation Profile
The concept of a "pain modulation profile" (PMP) is determined by an individual's balance between pain inhibition and facilitation.
Facilitatory and Excitatory Balance
often measured by Conditioned Pain Modulation (CPM) and Temporal Summation (TS) respectively. This profile can place individuals on a spectrum from pronociceptive (increased likelihood of experiencing pain) to antinociceptive (decreased likelihood). Evidence suggests that a pronociceptive profile, characterized by less efficient CPM and/or enhanced TS, is associated with various chronic pain syndromes. Importantly, the PMP is not static; it can be influenced by factors like surgery or pharmacological interventions, and may even predict the efficacy of certain pain treatments.
Endophenotypes
Researchers have also explored using neuroimaging techniques to identify "endophenotypes" for pain, which are measurable biological markers that could bridge the gap between the complex genetics of pain and the subjective experience of pain. There are various potential neuroimaging-based endophenotypes, including activity in the brainstem's descending modulatory system, concerted activity within cortical and subcortical networks (the "cerebral signature"), activity in the dorsal posterior insula as a potential primary nociception cortex, the prefrontal-limbic-brainstem network's role in emotional and cognitive aspects of pain, brain dynamics such as oscillations and resting-state networks, neurochemical changes like glutamate levels, and structural changes in the brain associated with chronic pain.
Pain Modulatory Endophenotypes include
- Temporal Summation
- Spatial Summation
- Conditioned Pain Modulation
- Context Related Analgesia (Placebo)
- Response to Tonic Pain Stimuli
- Offset Analgesia
- Stress Response (Analgesic - Hyperalgesic)
Endogenous Pain Modulation
Endogenous pain modulation (EPM) iinvolves a dynamic balance between pain inhibition and facilitation at all levels of the nervous system (peripheral, spinal, and supraspinal) and is closely integrated with the body's broader homeostatic controls, including cognitive, emotional, and autonomic pathways. Many patients with FGIDs, particularly IBS, exhibit abnormal EPM are often characterized by diminished pain inhibition or even pain facilitation compared to healthy individuals. Brain imaging studies support these findings, revealing different patterns of brain activation in key modulatory regions (frontal, limbic, and brainstem) in IBS patients during EPM engagement. An altered modulatory balance could be a unifying pathophysiological mechanism in FGIDs, potentially driven by both "top-down" (CNS-related) and "bottom-up" (peripheral, e.g., immune activation) factors.
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