From the Guidelines
Serotonin is the primary neurotransmitter that plays a crucial role in the descending modulation of pain. This monoamine neurotransmitter is released from neurons originating in the rostral ventromedial medulla and periaqueductal gray areas of the brainstem, which then project down to the dorsal horn of the spinal cord. When activated, these descending pathways inhibit pain transmission by reducing the release of excitatory neurotransmitters from primary afferent neurons and by hyperpolarizing second-order neurons in the pain pathway. Norepinephrine also contributes significantly to this pain control system, often working in conjunction with serotonin, as noted in the study by 1.
Some key points to consider in the management of pain include:
- The use of medications that increase serotonin and norepinephrine levels, such as duloxetine and venlafaxine, which are effective for treating various pain conditions, as seen in the study by 1.
- The endogenous opioid system also interacts with these serotonergic pathways, explaining why opioid medications activate this descending inhibitory system.
- Understanding this mechanism helps explain why antidepressants are often prescribed for chronic pain conditions even in the absence of depression.
- A multidisciplinary care team, including a psychologist with experience assessing and treating patients with chronic abdominal pain, is essential for the best and most effective assessment and treatment approach for patients with chronic pain, as recommended by 1.
The most recent and highest quality study, 1, published in 2024, highlights the importance of addressing the central factors that maintain and amplify pain, such as fear of pain or re-injury, and the role of serotonergic and noradrenergic brainstem nuclei in descending tonic pain modulation. Therefore, serotonin and norepinephrine are the key neurotransmitters involved in the descending modulation of pain, and medications that target these neurotransmitters, such as duloxetine and venlafaxine, are effective treatment options for various pain conditions.
From the Research
Neurotransmitters Involved in Pain Modulation
- Serotonin (5-HT) is a key neurotransmitter in the descending modulation of pain, as it targets receptors along the descending pain circuits and exerts either pro- or antinociceptive effects in different pain conditions 2, 3.
- Dopamine also plays a role in pain modulation, with descending dopaminergic pathways involved in the central regulation of chronic pain 4.
- Other neurotransmitters, such as norepinephrine, may also be involved in pain modulation, although their role is less well understood in the context of descending pain modulation.
Mechanisms of Action
- The descending serotonergic neurons in the raphe nuclei exert their effects by targeting receptors along the descending pain circuits, which can lead to either inhibition or facilitation of spinal nociceptive transmission 3.
- The effects of serotonin on pain modulation can be complex, with different subtypes of 5-HT receptors having different effects on pain transmission 3.
- Dopaminergic pathways may also interact with other neurotransmitter systems, such as the serotonergic system, to modulate pain perception 4.
Clinical Implications
- The use of medications that target the serotonergic system, such as selective serotonin reuptake inhibitors (SSRIs), may have potential applications in the treatment of chronic pain conditions, including chronic primary pain 2 and tension-type headache 5.
- However, the evidence for the effectiveness of SSRIs in preventing tension-type headache is limited, and more research is needed to fully understand their role in pain modulation 5.