Pain Facilitation and Inhibition

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Tips for writing this page:

  • Define and describe the differences between faciliatatory and inhibitory pathways, incluing their brain sites and neurotransmitters
  • Explain and describe how these pathways can be activated by non-pharmacological agents.

Original Editor - Manisha Shrestha

Top Contributors - Manisha Shrestha, Jo Etherton and Lauren Lopez  

ascending and descending tracts for pain pathways.Ascending tract-lateral spinothalamic tract. 1st order neuron from pheripheral tissue ( prostaglandins) to dorsal horn of spinal cord(substania gelatinosa). neurotransmitter is Substance P. 2nd order neuron from sustania gelatinosa to thalamus . then 3rd order neuron from thalamus to cortex (primary and secondary somatosensory cortex (S1 and S2, respectively), anterior- and mid-cingulate cortex (ACC and MCC, respectively) and insula.

endogenous pain inhibition-peri-acqueductal gray in mid brain.

to affect pain modulation including the thalamus, which seems to contribute to pain modulation via the mediodorsal (pain facilitation) and ventromedial (pain inhibition) nuclei.

rostroventromedial medulla (RVM) play important roles in descending modulation of nociception, which can result either in inhibition and/or facilitation of nociceptive and non-nociceptive inputs.

Descending pain pathway

Opioid pathway

Descending projections from the RVM extend to spinal cord dorsal horns where they connect to primary afferent terminals, second- and third-order neurons, as well as interneurons.

Serotonergic pathway

serotonin (5-HT) and norepinephrine, are involved in endogenous pain modulation [51,52]. Norepinephrine and 5-HT can be released via descending pain pathways to modulate nociceptive signaling in the spinal cord. Norepinephrine inhibits pain through α2 adrenoceptors, while 5-HT seems to have pain facilitatory and inhibitory functions.

RVM neurons that have glycinergic or GABAergic projections to the spinal cord to mediate antinociception. It appears, that descending serotonergic projections from the RVM are relevant for pain facilitation in chronic pain, but they are not involved in opioid-mediated inhibition of acute pain.

Noradrenergic pathways

Direct stimulation of PAG or RVM does not only increase 5-HT but also norepinephrine concentrations in the cerebrospinal fluid, resulting in pain reductions

Accumulating evidence supports the important role of CNS pain modulation for both analgesia and hyperalgesia. Multiple cortical and subcortical brain and brainstem regions integrate and process sensory, autonomic and emotional information, resulting in activation of the PAG and RVM, with subsequent inhibition or facilitation of pain-related dorsal horn neurons. This top–down modulation is relevant for experimental, as well as clinical pain, and influences the effects of pain-relieving drugs, such as opioids, NSAIDs, 5-HT–norepinephrine-reuptake inhibitors and gabapentinoids. These pain modulatory pathways are affected by memories and mood, as well as sociocultural background.[1]

Facilitatory Pathways


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Inhibitory Pathways

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  1. Staud R. The important role of CNS facilitation and inhibition for chronic pain. International journal of clinical rheumatology. 2013 Dec 1;8(6):639.
  2. Armando Hasudungan. PAIN! Physiology - The Ascending Pathway, Descending Pain Pathway and the Substantia Gelatinosa. Available From: [last accessed 22/2/2020]