Unlike prescription painkillers, the many alkaloids in kratom treat pain differently — offering more well-rounded analgesic effects:
Mu-, kappa-, and delta-opioid pain receptors — These receptors act as the primary gatekeepers for the pain signals traveling toward the brain. 7-hydroxymitragynine, mitragynine, and speciociliatine have the strongest action on these receptors.
Adrenergic receptors — The ɑ1 and ɑ2 adrenergic receptors are involved in both the modulation and interpretation of pain signals in the brain. Adrenergic agonists are often used as alternative painkillers when opiate drugs are inappropriate.
Calcium channels — Some alkaloids, such as corynanthine, have been shown to inhibit calcium ion channels. This action reduces pain signal transduction, and medications with this effect are sometimes used as an alternative option to opioid painkillers in the hospital setting.
Dopamine — Ajmalicine and corynantheidine have the strongest impact on these neurotransmitters. Dopamine and serotonin are less involved with pain than the opiate receptors or adrenergic receptors, but both are involved with the interpretation and downstream effects pain has on the body.
Serotonin — The exact role of serotonin in the pain response is not well understood, but studies have shown that increasing serotonin activity can reduce pain sensitivity and increase tolerance to pain. Isopteropodine and epicatechin have both been shown to modulate serotonergic function in the brain.
COX, phosphodiesterase, and lipopolysaccharide — Mitraphylline, epicatechin, and rhynchophylline each interact with these various enzymes to limit inflammation and reduce chronic pain.
Metabolic Competitors — Most alkaloids in kratom compete for the same liver enzymes tasked with breaking them down. This effect prolongs the duration of effects and enhances the potency of powerful kratom alkaloids such as 7-hydroxymitragynine.
Neuroprotectants — Compounds like corynoxine A and corynoxine B act as neuroprotectants to support the recovery of damaged neurons that may be causing pain.
Muscle Relaxants — Both mitraphylline & speciogynine act as a muscle-relaxants to support muscle tension-related pain.
All these pathways are involved in the transmission, interpretation, and somatic expression of pain in various ways.
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