PHYSIOLOGICAL MECHANISMS OF THE PAIN REFLEX AND NATURAL ANALGESIC INHIBITION: FROM GATE CONTROL TO DESCENDING MODULATION

Nguyen Thanh Lam1, Phan Thanh Tai2, Nguyen Kim Vuong2
1 Vo Truong Toan University
2 Vo Truong Toan University Hospital

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Abstract

Objective: To synthesize core physiological mechanisms underlying nociceptive reflexes and the body’s natural pain-inhibitory systems, and to appraise non‑pharmacologic strategies that harness endogenous analgesia.


Method: We narratively reviewed landmark primary studies and authoritative reviews on pain physiology and modulation covering gate control, spinal-brainstem descending systems, diffuse noxious inhibitory controls/conditioned pain modulation, placebo/opioid‑dependent mechanisms, mindfulness‑related analgesia, exercise‑induced hypoalgesia, and transcutaneous electrical nerve stimulation. Selection prioritized highly cited, peer‑reviewed works with mechanistic clarity and human relevance.


Results: Pain reflexes arise from activation of peripheral nociceptors with segmental spinal integration and rapid protective motor outputs; perception is shaped by ascending-descending interactions. Endogenous inhibition involves segmental gating in the dorsal horn, and supraspinal control via periaqueductal gray-rostral ventromedial medulla and locus coeruleus that project to the dorsal horn through opioidergic, serotonergic, and noradrenergic pathways. DNIC/conditioned pain modulation indexes the integrity of these systems. Psychobiological factors including expectation (placebo), attention/mindfulness, and acute exercise recruit overlapping modulatory circuits. Noninvasive somatosensory input (e.g., TENS) engages large‑fiber gating and descending inhibition.


Conclusion: Natural analgesic inhibition is multi‑layered segmental, brainstem, and cortical and can be amplified with behavioral and sensory interventions. Understanding these mechanisms supports rational, low‑risk, multimodal approaches to pain management and provides physiological endpoints (e.g., conditioned pain modulation) for phenotyping and treatment tailoring.

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References

[1] Raja S.N, Carr D.B, Cohen M et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain, 2020, 161 (9): 1976-1982. DOI: 10.1097/j.pain.0000000000001939
[2] Melzack R, Wall P.D. Pain mechanisms: a new theory. Science, 1965, 150 (3699): 971-979. DOI: 10.1126/science.150.3699.971
[3] Basbaum A.I, Fields H.L. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annual Review of Neuroscience, 1984, 7: 309-338. https://psycnet.apa.org/doi/10.1146/annurev.ne.07.030184.001521
[4] Millan M.J. Descending control of pain. Progress in Neurobiology, 2002, 66 (6): 355-474. DOI: 10.1016/s0301-0082(02)00009-6
[5] Ossipov M.H, Dussor G.O, Porreca F. Central modulation of pain. Journal of Clinical Investigation, 2010, 120 (11): 3779-3787. DOI: 10.1172/JCI43766
[6] Le Bars D, Dickenson A.H, Besson J.M. Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain, 1979, 6 (3): 283-304. DOI: 10.1016/0304-3959(79)90049-6
[7] Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Current Opinion in Anaesthesiology, 2010, 23 (5): 611-615. DOI: 10.1097/ACO.0b013e32833c348b
[8] Zeidan F, Martucci K.T, Kraft R.A, Gordon N.S, McHaffie J.G, Coghill R.C. Brain mechanisms supporting the modulation of pain by mindfulness meditation. Journal of Neuroscience, 2011, 31 (14): 5540-5548. doi: 10.1523/JNEUROSCI.5791-10.2011
[9] Naugle K.M, Fillingim R.B, Riley J.L. A meta-analytic review of the hypoalgesic effects of exercise. Journal of Pain, 2012, 13 (12): 1139-1150. DOI: 10.1016/j.jpain.2012.09.006
[10] Sluka K.A, Walsh D. Transcutaneous electrical nerve stimulation: basic science mechanisms and clinical effectiveness. The Journal of Pain, 2003, 4 (3): 109-121. DOI: 10.1054/jpai.2003.434