From the Guidelines
Descending inhibition is a critical pain modulation mechanism that involves higher brain centers, such as the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM), suppressing pain signals at the spinal cord level, and deep brain stimulation (DBS) targeting these regions has proven effective in treating refractory neuropathic pain syndromes. The process of descending inhibition primarily originates in the PAG of the midbrain and the RVM in the brainstem, and when stimulated, these areas activate descending pathways that release neurotransmitters including serotonin, norepinephrine, and endogenous opioids like enkephalins and endorphins 1. These neurotransmitters act on the dorsal horn of the spinal cord, where they inhibit pain transmission by hyperpolarizing primary afferent terminals and second-order neurons, reducing the release of excitatory neurotransmitters like substance P and glutamate. This inhibition occurs through activation of μ-opioid receptors, α2-adrenergic receptors, and GABA receptors in the spinal cord, resulting in decreased pain signal transmission to higher brain centers. Some key clinical pain syndromes that DBS is effective in treating include complex regional pain syndrome (CRPS), which is a refractory neuropathic pain syndrome that can be effectively managed with DBS, particularly when targeting the PAG and thalamus, as shown in recent studies 2. In CRPS patients, DBS can normalize aberrant neural activity and enhance endogenous pain inhibition, providing significant pain relief when conventional treatments have failed. The effectiveness of DBS in treating CRPS and other refractory neuropathic pain syndromes highlights the importance of descending inhibition in pain modulation and the potential of DBS as a therapeutic option for patients with severe and refractory pain. Key areas of the brain that need to be stimulated for effective pain relief include the PAG, RVM, and thalamus, which are involved in the descending pain inhibitory pathway. The neurotransmitter systems involved in the effect of DBS on pain modulation include the serotonergic, noradrenergic, and opioidergic systems, which play a crucial role in inhibiting pain transmission at the spinal cord level. Overall, DBS is a promising treatment option for refractory neuropathic pain syndromes, and its effectiveness is supported by recent studies, including those published in reputable journals such as Nature Reviews Disease Primers 2.
From the Research
Descending Inhibition Mechanisms
The precise mechanisms involved in descending inhibition highlight the importance of stimulating specific areas of the brain to modulate pain perception.
- The periaqueductal gray (PAG) and periventricular gray (PVG) matter are key targets for deep brain stimulation (DBS) in treating severe, refractory neuropathic pain 3, 4.
- The ventral posterior thalamus is another area targeted by DBS for chronic pain management 3, 5.
- The rostral anterior cingulate cortex (Cg24) has also been identified as a potential target for DBS in treating chronic pain 3.
Neurotransmitter Systems
The neurotransmitter systems involved in the effect of DBS on pain modulation include:
- Endogenous opioids, which are released by DBS of the PAG and contribute to its analgesic effect 6.
- Other neurotransmitter systems, such as those involved in the affective sphere of pain, which have emerged as plausible alternatives for modulation by DBS 5.
Impact on Lower Neural Centers
The impact of DBS on lower neural centers, such as the spinal cord, is not fully understood. However, studies suggest that DBS can modulate pain perception by influencing the activity of spinal cord neurons 7.
- DBS has been shown to be effective in treating various clinical pain syndromes, including: + Neuropathic facial pain 4. + Post-stroke pain 3, 5. + Phantom limb pain 3, 5, 6. + Brachial plexus injury 3, 5. + Anesthesia dolorosa 3, 6.
Clinical Applications
DBS has been used to treat various debilitating conditions, including: