Acupuncture Provides Pain Relief—How?

Acupuncture is an ancient medicinal system used to treat a wide variety of diseases and health challenges. Based upon a patient’s chief complaint and overall health, a practitioner selects acupuncture points (acupoints) and inserts acupuncture needles to the appropriate depth for each acupoint (ranging from 4 to 25 mm). Needles are typically manipulated until a sensation is elicited. This sensation is referred to as “de qi” and is typically described as a full, warm, aching, or heavy feeling at the site of needling. Needles are then left in place from seconds to minutes or may be additionally stimulated for a period using heat or electrical current (electroacupuncture).

Research suggests that acupuncture points correspond to specific locations on the body that contain greater-than-average amounts of peripheral nerves, blood vessels (which are rich in sympathetic nerves), and/or free nerve endings and sensory receptors of afferent nerve fibres.1, 2, 3, 4, 5 It is thought that needle insertion and stimulation at these sites causes local tissue changes and stimulates the immune system and the nervous system, resulting in functional changes throughout the entire body.6

These changes appear to have analgesic effects, providing both short-term and long-term pain relief. Research suggests acupuncture provides pain relief by influencing body-system functioning at the area being needled (locally), at the level of the spinal column (dorsal horn), and at the supraspinal level (the brain).7, 8

Local Pain Modulation

Both physical insertion and stimulation of an acupuncture needle at an acupoint appear to influence the surrounding tissue in a variety of ways, all of which result in diminished local (and perhaps distal) pain sensation and severity.

Axon Reflex

Needle insertion and stimulation appear to very quickly trigger the “axon reflex,” a local nerve-mediated response to tissue injury.9, 10 Physical trauma—or, in the case of acupuncture, needle insertion—stimulates local nerves to release chemical messengers which trigger local capillaries to vasodilate and increase circulation to the affected area. Immune cells—especially mast cells and platelets—respond to this site and release more chemical messengers, including substance P and histamine. This in turn creates a local inflammatory response and prompts further blood flow to the needled site.7, 11, 12

This localized increase in circulation, immune cells, and resulting inflammation can be visualized by local hyperemia (redness) or wheal(s) forming at the site of the needle insertion, which may spread outwards by a few millimetres to a few centimetres, depending upon the strength of the local axon reflex response.7 This response is also thought to help stimulate healing and reduce long-term inflammation, thus contributing to long-lasting relief and local pain resolution.9, 11

Production of Inhibitory Mediators

A wide variety of chemical mediators are produced in response to tissue disruption and damage, but it is thought that, because needle insertion and stimulation causes minimal tissue damage, predominantly inhibitory mediators are produced when an acupoint is needled.6, 13 Needle insertion appears to increase local levels of norepinephrine, beta-endorphin, somatostatin, and acetylcholine, while stimulation (either mechanically or electrically) appears to increase ATP and adenosine levels.13, 14, 15, 16, 17, 18, 19

These chemicals all appear to have an inhibitory effect upon afferent nerve stimulation, which decreases the amount of afferent input reaching the spinal column, thus the reducing conscious perception of pain. This production of local inhibitory neurotransmitters and subsequent downregulation of nervous input to the spinal cord also appear to affect sensation and pain perception distal to the acupoint needled; this may in part explain how needling proximal to an area of pain appears to diminish the severity of pain at a distal site.20

There is also speculation that the release of vascular and neural mediators from the needled area may influence local nerves from different spinal segments, thus expanding afferent input modulation to multiple spinal levels and broadening acupuncture’s local therapeutic effect.6

Electroacupuncture: Local Effects

The application of electricity to inserted acupuncture needles appears to further promote local pain modulation.8 In particular, electroacupuncture appears to stimulate immune cells to release endogenous opioids, especially beta-endorphin and met-enkephalin, which then bind to opioid receptors on peripheral nerves and suppress pain transmission.8, 9 Electroacupuncture also appears to activate sympathetic nerve fibres, which inhibits pain perception, but the mechanism of action behind this effect remains unclear.8

Pain Modulation at the Spinal Cord

Acupuncture appears to modulate pain transmission at the level of the spinal cord through a number of mechanisms, all of which appear to act by diminishing the strength or frequency with which noxious stimuli from the peripheral nervous system is transmitted to supraspinal levels for processing and pain perception.7, 21, 22

Descending Noxious Inhibitory System

Multiple studies suggest that acupuncture activates the “descending noxious inhibitory system,” a system by which the input of noxious stimuli (pain) is detected by supraspinal regions (in the brain), which then almost instantaneously send signals down to the dorsal horn of the spinal cord to suppress further pain transmission.7, 21, 22

The first step in this system requires the activation of afferent A delta and C fibres; they need to detect a noxious stimuli.7, 23, 24, 25 As discussed above, acupuncture needles are typically inserted to target depth and physically stimulated until “de qi” is felt.7, 11 The feeling of “de qi” is thought to reflect the activation of A delta and C fibres, as activation of these nerves are associated with aching, soreness, and/or a feeling of warmth, similar to the feeling of “de qi.”7, 23, 24

Once activated, A delta and C fibres synapse with ascending neurons at the dorsal horn of the spinal cord and transmit noxious stimuli up to the brain.7, 23, 24 This noxious stimuli is relayed up the spine via the spinothalamic and spinoreticular tracts, which then activates the locus coeruleus (LC) and the periaqueductal grey (PAG)‑nucleus raphe magnus (NRM) descending spinal pathways.8, 21, 22 These two descending pathways send different inhibitory signals to the dorsal horn and thus reduce further A delta and C fibre input from ascending to the brain.21, 22

The LC, when activated, sends a signal down the spinal cord which stimulates the release of norepinephrine. Norepinephrine binds to alpha 2 adrenoceptors on the primary afferents (pain-bearing A delta or C fibres), just before the synaptic junction with the ascending postganglionic neurons at the dorsal horn of the spinal cord. This inhibits the release of glutamate from the afferent nerves, thus reducing the capacity of those stimulated afferent nerves to transmit their noxious (pain) input to the spinal nerves.8, 26

Comparatively, the PAG‑NRM descending pathway releases serotonin upon the postsynaptic neurons in the dorsal horn where the activated A delta and C fibres synapse. This release of serotonin acts locally on the spinal cord and reduces the frequency of ascending noxious input reaching the brain.8, 26 There is some speculation as well that this “serotonergic descending pathway” may trigger opioid release locally in the spinal cord.8

Thus, the activation of the descending noxious inhibitory system through both the LC and the PAG‑NRM pathway results in diminished pain perception by diminishing synaptic transmission and modulating ascending signals at the level of input to the spinal cord.6

While acupuncture provides afferent input at specific spinal levels (depending upon the acupoint chosen), there is speculation that this downward modulation of dorsal-horn transmission may affect multiple spinal levels, resulting in a reduction in ascending pain signals throughout the body.6, 26

Electro Acupuncture: Spinal Cord Influences

Depression of neural excitability at the level of the dorsal horn of the spinal cord appears to be further modulated by electroacupuncture, which may have a more sustained analgesic response than that afforded by the descending noxious inhibitory system.

Electroacupuncture in particular appears to increase endogenous opioid production in the spinal cord and the brain.6, 7, 27, 28 This effect can take time; production increases after 15 minutes of electroacupuncture and continues for 5 to 15 minutes more; electroacupuncture past 30 minutes does not appear to further increase endogenous opioid levels.7 The specific opioids produced also appear to be frequency-dependent; electroacupuncture performed at 2 Hz appears to promote the production or release of endomorphin and enkephalin at the level of the spinal cord, while electroacupuncture at 100 Hz appears to promote the release of dynorphin.7, 8, 11, 26

Increased endogenous opioids also appear to decrease levels of substance P in the spinal cord, a chemical mediator commonly associated with inflammation and pain.8, 9 Opioids also appear to decrease the production or release of excitatory amino acids such as glutamate in the spinal cord, thus acting to decrease upward pain transmission at the level of the spinal cord.8

Effects Upon Brain Activity and Pain Perception

Acupuncture appears to influence higher-level cortical activity—both the subjective and affective experience of pain—but the exact mechanism(s) behind this and/or brain locations influenced is/are unclear.9, 29

Changes in Pain Perception

Functional magnetic resonance imaging shows that acupuncture result in nonspecific activation of many brain regions, with some areas more clearly involved than others.6, 8 Almost immediately after an acupuncture needle is inserted, brain areas involved in pain processing are activated in a positive response; as the treatment continues, this response becomes negative, perhaps indicating a brain-level analgesic effect.13 Other studies suggest the long-term analgesic effects from acupuncture (especially electroacupuncture) are due to the pain perception of the mesolimbic system being “reset.”11 Unfortunately, the effect of acupuncture on cortical processing and pain perception has thus far been minimally researched.

Increased Levels of Endogenous Opioids

As previously discussed, acupuncture, especially electroacupuncture, appears to increase endogenous opioid levels throughout spinal-cord and supraspinal regions.8, 29 There is speculation that increased levels of opioids in anterior cingulate cortex could change the affective experience of pain—making pain less emotionally unpleasant and thus more bearable. It also appears that increased levels of endogenous opioids—especially released following electroacupuncture—activate mu opioid receptors in GABAergic neurons, which suppresses GABA release. This reduces GABA-induced suppression of the rostral ventromedial medulla (RVM), which then increases activity of descending serotonergic neurons from the RVM to the spinal cord and modulates pain transmission at the spinal level in a similar (but different) way as the descending noxious inhibitory system.8

Pituitary Gland Stimulation

While the preceding pathway isn’t clearly understood, it appears that acupuncture prompts the pituitary gland to increase secretion of adrenocorticotropic hormone (ACTH), which then travels to the adrenal glands and triggers cortisol release.8, 11 Increasing cortisol levels has a systemic anti-inflammatory effect, and also results in the downregulation of COX‑2 (an enzyme which produces inflammatory mediators).

This appears to result in a reduction of inflammatory cytokine production—especially PGE2 levels, an inflammatory cytokine produced by COX‑2. Downregulation of COX‑2 also appears to increase levels of anandamide, an endogenous cannabinoid, and promote an increase in CB2 cannabinoid receptors, resulting in further pain modulation.8

Conclusion

Acupuncture appears to provide both short- and long-term pain relief through multiple complex and often intersecting mechanisms, both locally at the site of needle insertion and systemically. Needling appears to exert a local pain-relieving effect by increasing blood flow and promote the release of inflammatory mediators (via the axon reflex), while also promoting the production of inhibitory mediators that reduce activation of pain-sensing nerves within the tissues needled. Acupuncture appears to almost instantly modulate the transmission of noxious (pain) stimuli from the periphery to the brain by reducing transmission at the dorsal horn of the spinal cord, with further sustained effects when electroacupuncture is applied for 15–30 minutes. Acupuncture also appears to decrease inflammation systemically by influencing hormone secretion from the pituitary and adrenal glands. Finally, acupuncture appears to influence the conscious perception of pain through a variety of not-well-understood mechanisms.