Pain Facilitation and Inhibition

Original Editor - Manisha Shrestha

Top Contributors - Manisha Shrestha, Lucinda hampton, Jo Etherton, Kim Jackson, Lauren Lopez, Tolulope Adeniji and Kirenga Bamurange Liliane  

Introduction

Pain experience

The pain experience among people is highly variable, even under circumstances where the soft tissue injuries are similar. The individual difference in pain sensitivity is related to sensitivity of peripheral pain receptors and variability in CNS pain processing. Reasons for this include:

1. Peripheral impulses coming from tissue receptors undergo modification in dorsal horn neurons that can either result in inhibition or facilitation of pain.
2. Emotional state, level of anxiety, attention and distraction, memories, stress, fatigue and many other factors can either increase or reduce the pain experience.

Increasing evidence suggests that ‘bottom–up’ and ‘top–down’ modulatory circuits within the spinal cord and brain play an important role in pain processing, which can profoundly affect the experience of pain.

Ascending pain pathway

Ascending pathway is how we feel pain.

1. The process begins when pain sensory neurons, called nociceptors, detect a potentially damaging stimulus. These neurons send this signal as an action potential to other neurons using the excitatory neurotransmitters glutamate, which depolarizes the cell, and substance p, which promotes inflammation and pain.
2. Once the signal reaches the base of dorsal horn, a column in the spinal cord that relays sensory information, it is then sent up though a network of neurons called the spinothalamic tract that delivers sensory signals from the spinal cord to the somatosensory cortex which perceives pain.

Descending pain pathway

Once the signal from the ascending pathway reaches the somatosensory cortex, it triggers the descending pain modulation pathway. The goal of this pathway is to allow the organism to function enough to respond to the pain source by reducing the pain signal through neuronal inhibition. Descending pain control pathways can be both facilitatory as well as inhibitory.

1. Facilitatory pathways are the one which enhances pain perception
2. Inhibitory pathways suppresses pain perception.

The balance between inhibition and facilitation is dynamic, and can be altered in different behavioral, emotional, psychological and pathological states. Descending pain control pathways plays a critical role in determining the experience of both acute and chronic pain. Facilitatory and inhibitory pathways are further described below.

Picture showing supraspinal pain control sites.

The goal of this pathway is to allow the organism to function enough to respond to the pain source by reducing the pain signal through neuronal inhibition.

1. It begins in the periaqueductal gray (PAG), a region of the midbrain that process nociceptive information and relays it to the rostral ventral medulla (RVM).
2. These neurons in the RVM then send a signal down the spinal cord to release endogenous opioids at neuronal synapses at multiple points in the peripheral nervous system to prevent these pain signaling neurons from sending action potentials.
3. Additionally, these endogenous opioids are released in parts of the dorsal horn of the spinal cord to further block ascending pain transmission signals.

Pain is helpful since it alerts the brain to tissue damage and provides useful information about its type and location. However, when this signal starts to impede our own ability to survive and function it must be reduced, hence the need for the descending pathway and endogenous opioids.

Based on Neurotransmitters:

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. Descending inhibitory function of the RVM is associated with OFF-cell activity, which can be significantly upregulated by endogenous opioids. Neuroimaging studies have demonstrated that placebo analgesia is dependent on activation of pain inhibitory systems from cortical and subcortical areas, including the rostral ACC and PAG. Increased activation of these brain areas seems to be associated with placebo analgesia.

Serotonergic pathway

Serotonin (5-HT) and norepinephrine, are involved in endogenous pain modulation. 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.

Depending on the receptor subtype, spinal 5-HT can have inhibitory or facilitatory effects on pain. For example, spinal blockade of inhibitory 5-HT receptors abolished the antinociceptive effect of morphine injections into the RVM, while blockade of pain facilitatory 5-HT receptors prevented hyperalgesia.

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 Although neither PAG nor RVM contain noradrenergic neurons, both regions communicate with norad - renergic brain stem nuclei associated with pain modulation, including the locus coeruleus. These nuclei have noradrenergic projections to the spinal cord, which can inhibit the response of dorsal horn pain transmission neurons.Dorsal horn neuron recordings have shown that activated a2-adrenergic receptors hyperpolarize presynaptic neurons and decrease the release of excitatory neu - rotransmitters from primary afferent terminals, resulting in pain inhibition.

Non-pharmacological agents affecting pain modulation

Non- pharmacological agents are the other agents than that of medication which affect the pain modulation systems.

Nonpharmacological approaches to the relief of pain are

• psychological interventions (including distraction, stress management, hypnosis, and other cognitive-behavioral interventions),
• acupuncture and acupressure,
• transcutaneous electrical nerve stimulation,
• physical therapies (including massage, heat/cold, physiotherapy, osteopathy, and chiropractic).

Accumulating evidence supports the important role of supraspinal 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. These pain modulatory pathways are affected by memories and mood, as well as sociocultural background as different cortical regions like amygdala, hypothalamus are involved in the descending pain modulation pathways.

Nonpharmacological analgesia therefore involves the inhibition of nociceptive input by activating separate antinociceptive outputs. Electroacupuncture has been shown to enhance the expression of serotonin and reduce the release of substance P during electroacupuncture inhibition of acute nociceptive responses.TENS appears to produce both segmental and descending pain inhibition since inhibition remains after spinalization (removal of descending inhibition) and concentrations of endogenous opioids have been shown to increase in cerebrospinal fluid following TENS procedure.