Impétigo

5-HTP is a serotonin precursor studied in fibromyalgia and chronic pain syndromes. Two clinical trials including a double-blind placebo-controlled study found 300 mg/day 5-HTP improved tender points, pain scores, anxiety, and sleep in fibromyalgia. It modulates central pain sensitization via serotonergic pathways.

Analgesic activity has been confirmed in in vivo preclinical studies and is listed among the documented pharmacological properties of A. spectabilis in the peer-reviewed review literature. The 2021 review confirms analgesic activity alongside antitussive and anti-inflammatory findings.

Acetyl-L-carnitine (ALC) has been studied for neuropathic chronic pain through modulation of neurotransmitter activity, promotion of nerve regeneration, and mitochondrial energy support. RCT evidence supports its use as an adjunct for fibromyalgia and peripheral neuropathic pain. A randomized controlled study showed ALC combined with PEA synergistically improved fibromyalgia pain.

Alpha-lipoic acid (ALA) is a potent antioxidant studied extensively for neuropathic chronic pain, particularly diabetic peripheral neuropathy. Multiple meta-analyses show significant pain reduction. It reduces oxidative stress in nerve tissue, improves nerve conduction velocity, and is recognized by neurological guidelines for diabetic neuropathy.

Topical arnica preparations have analgesic and anti-inflammatory properties studied in osteoarthritis and post-operative pain. A Cochrane review acknowledged some evidence for topical arnica gel in chronic pain. A rater-blinded trial found arnica gel equivalent to ibuprofen gel for hand OA pain.

Benfotiamine has demonstrated analgesic effects in both diabetic and non-diabetic neuropathic pain in animal models, reducing tactile allodynia and inflammatory nociception. Clinically, it has been used for painful diabetic neuropathy and alcoholic polyneuropathy. The BEDIP trial (n=40) showed significant improvement in neuropathy pain scores after 3 weeks at 400 mg/day.

A. scholaris alkaloids exert analgesic effects in multiple preclinical pain models including acetic acid-induced writhing, hot-plate test, formalin test, and neuropathic pain (chronic constriction injury of sciatic nerve) in rodents. Both central and peripheral analgesic mechanisms have been proposed, with COX/LOX inhibition as the likely peripheral pathway.

Boswellic acids from Boswellia serrata inhibit 5-lipoxygenase (5-LOX), reducing leukotriene-driven inflammation. Multiple randomized controlled trials and a 2014 Cochrane review found modest but meaningful benefits for osteoarthritis and chronic inflammatory pain. Ayurvedic medicine has used this resin for centuries to treat inflammatory conditions.

Boswellic acids are the active analgesic and anti-inflammatory constituents of Boswellia serrata resin, specifically inhibiting 5-LOX. RCTs in knee osteoarthritis demonstrate significant reductions in pain and improvement in joint function. Both traditional Ayurvedic medicine and modern clinical evidence support their use for chronic inflammatory pain.

Bromelain has documented analgesic properties in human clinical studies including inflammatory pain, urogenital inflammation, post-surgical pain, and chronic arthritis. It acts directly on pain mediators such as bradykinin, reduces plasma kininogen, and inhibits PGE2. Multiple PMC reviews and clinical trials confirm its use in chronic pain settings.

C. crista seed extracts demonstrate analgesic activity in multiple preclinical pain models including writhing reflex and tail immersion tests. Anti-inflammatory properties complement the analgesic activity. Traditional use for pain management is well documented.

DHA and EPA reduce chronic pain-related inflammatory mediators via competitive inhibition of arachidonic acid pathways. Preclinical studies with pure DHA demonstrate significant reductions in arthritic pain and joint edema. Clinical evidence in rheumatoid arthritis and inflammatory rheumatic diseases supports modest analgesic effects of omega-3 supplementation.

Health Canada has authorized a standardized E. californica preparation (3 g dried herb, 0.8% isoquinoline alkaloids) as an analgesic and co-analgesic for chronic pain management. An open-label clinical trial confirmed that California poppy can be used as a co-analgesic for chronic pain and for pain-related insomnia. Animal studies also support analgesic activity including for sciatic nerve pain and osteoarthritis models.

Camphor is a recognized OTC topical analgesic ingredient with a scientifically characterized mechanism (TRPV1 desensitization, TRPA1 blockade) for reducing chronic musculoskeletal pain. Human studies and clinical case series confirm analgesic efficacy. A 2016 study cited by Medical News Today showed camphor oil reduced chronic lower back pain.

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid from Cannabis sativa with analgesic and anti-inflammatory properties mediated via TRPV-1, 5-HT1A, and CB1 receptors. A 2024 systematic review of 40 studies found sufficient clinical and preclinical evidence for CBD in pain treatment. Evidence is strongest for neuropathic and osteoarthritis pain.

Capsaicin, the pungent compound in chili peppers, desensitizes TRPV1 nociceptors and depletes substance P. A 2016 Cochrane review of 14 RCTs (2,050 participants) found capsicum/capsaicin reduced chronic pain more than placebo, including for low back pain and neuropathic pain. It is FDA-cleared in an 8% patch form for postherpetic neuralgia.

Capsaicin is among the most extensively clinically validated natural analgesics for chronic pain. A high-concentration (8%) capsaicin patch (Qutenza) is FDA-approved for neuropathic pain. Multiple RCTs and systematic reviews confirm benefit for postherpetic neuralgia, diabetic neuropathy, and other chronic pain conditions.

Capsicum (chili pepper genus) contains capsaicin and capsaicinoids that reduce chronic pain by TRPV1 desensitization. A 2016 Cochrane review confirmed topical Capsicum frutescens reduces chronic low-back pain more than placebo across multiple RCTs. The NCCIH recognizes capsicum among evidence-supported herbal approaches to chronic pain.

BCP selectively activates CB2 receptors to reduce both inflammatory and neuropathic pain in multiple preclinical models, including formalin, sciatic nerve ligation, chemotherapy-induced neuropathy, and diabetic neuropathy. Effects are CB2-dependent and do not involve the psychotropic CB1 receptor.

Cat's Claw (Uncaria tomentosa) modulates immune function and reduces inflammatory cytokines through oxindole alkaloid and pentacyclic triterpene content. Small human studies have shown possible benefit in osteoarthritis and rheumatoid arthritis chronic pain. Traditional Amazonian medicine has used it for inflammatory joint conditions for centuries.

Topical capsaicin is among the most evidence-backed non-opioid topical analgesics for chronic pain conditions. Cochrane reviews, multiple RCTs, and a prescription-approved 8% patch support its use for postherpetic neuralgia, diabetic neuropathy, and musculoskeletal pain. The mechanism is well-characterised: C-fibre desensitisation via substance P depletion.

Chondroitin sulfate is a major structural component of cartilage used for osteoarthritis chronic pain. Evidence is mixed but a conditional recommendation exists for hand OA from the Arthritis Foundation. It has mild anti-inflammatory effects and may slow cartilage degradation. The NCCIH notes it as a widely used supplement for OA-related pain.

CQ demonstrates peripheral and central analgesic activity in preclinical models, inhibiting COX-1, COX-2, and 5-LOX pathways. The Bloomer 2013 human pilot study showed a ~33% reduction in chronic exercise-related joint pain after 8 weeks. Animal studies with neuropathic pain models also show significant antihyperalgesic effects of CQ extracts.

Multiple Clematis species exhibit antinociceptive (pain-relieving) activity in animal models. Vitalboside from C. vitalba, C. brachiata aqueous extract, and SKI306X (containing C. mandshurica) have all demonstrated analgesic effects in validated rodent pain models. SKI306X showed non-inferiority to celecoxib for pain relief in RA patients in a Phase III trial.

Eugenol from clove is a clinically recognized analgesic, FDA-approved for dental use. It blocks voltage-gated sodium channels and TRPV1 pain receptors, and a human RCT confirmed eugenol paste outperformed alternatives for post-surgical dental pain and healing.

EPA and DHA reduce neuroinflammatory signaling that sensitizes pain pathways. In RA patients, cod liver oil significantly reduced pain intensity (67.5% reduction in one study). Omega-3 supplementation has broader evidence for reducing chronic pain across musculoskeletal and inflammatory pain conditions.

Coix seed polysaccharides demonstrate analgesic effects in animal models, reducing writhing responses and increasing pain thresholds. In TCM, coix seed is listed as an analgesic for neuralgia and joint pain.

Hydrolyzed collagen (collagen peptides) supplementation reduces chronic joint pain in osteoarthritis and activity-related joint pain. RCTs show significant reductions in OA knee pain and improved function. Collagen peptides stimulate chondrocyte collagen synthesis and are recognized as a joint health supplement for chronic musculoskeletal pain.

Topical comfrey preparations are clinically proven for chronic painful conditions including degenerative osteoarthritis. RCTs in knee OA lasting up to 12 weeks demonstrate sustained pain reduction. Post-marketing surveillance found patients with longstanding joint and muscle pain (average 6.5 years prior to enrolment in one knee OA study) experienced significant improvement. ESCOP and the German Commission E recognise comfrey for painful musculoskeletal conditions.

Commiphora myrrh contains furanosesquiterpenes that act on opioid receptors, producing analgesic effects documented in animal studies and supported by preliminary human observations. Commission E and ESCOP recognize anti-inflammatory and analgesic properties underpinning topical pain relief.

Coenzyme Q10 (CoQ10) supplementation has shown efficacy in migraine prevention and fibromyalgia-related chronic pain in multiple clinical trials, including RCTs. It reduces mitochondrial oxidative stress and inflammation. At 150–300 mg/day, it decreases migraine frequency, headache days, and nausea.

Corydalis (Yan Hu Suo) is used in Traditional Chinese Medicine as a potent analgesic for chronic pain. Its primary active alkaloid, tetrahydropalmatine (THP/L-THP), modulates dopamine D1/D2 receptors and opioid receptors to produce analgesia. Clinical studies have demonstrated THP's analgesic effects in neuralgia, dysmenorrhea, headaches, and chronic musculoskeletal pain.

Curcumin, the principal bioactive compound in turmeric, inhibits NF-κB and COX-2 inflammatory pathways. Multiple RCTs show it reduces osteoarthritis pain comparably to ibuprofen, with better GI tolerability. Both Ayurvedic tradition and modern systematic reviews support its use for chronic inflammatory pain.

Devil's Claw (Harpagophytum procumbens) root contains harpagoside, an iridoid glycoside that inhibits COX-2 and NF-κB. A Cochrane review found standardized daily doses of 50–100 mg harpagoside reduced chronic low-back pain more than placebo, with one trial showing equivalence to 12.5 mg rofecoxib. More than 50 human studies support its analgesic effects.

DHA is the principal structural omega-3 fatty acid in neural membranes and a precursor to D-series resolvins and protectins that resolve neuroinflammation. Combined EPA+DHA supplementation is supported by systematic review evidence for chronic pain reduction (SMD −0.55). DHA modulates inflammatory signaling relevant to neuropathic and musculoskeletal chronic pain.

DMSO is an organosulfur compound used topically for musculoskeletal and neuropathic chronic pain. It penetrates skin readily, carrying analgesic anti-inflammatory agents and possessing intrinsic anti-inflammatory and free radical scavenging activity. The NCCIH and FDA recognize topical DMSO for interstitial cystitis pain; it has been studied for OA and low-back pain.

EGCG is under investigation as an anti-nociceptive agent, addressing nociceptive, neuropathic, and nociplastic pain through anti-inflammatory, antioxidant, and neuroprotective mechanisms. A 2025 systematic review identified it as a promising adjunct to conventional pain management, though clinical bioavailability limitations constrain translation.

EPA is a long-chain omega-3 fatty acid that reduces chronic pain by competing with arachidonic acid for COX/LOX enzymes, lowering pro-inflammatory prostaglandin E2 and leukotriene B4. It also serves as a precursor to anti-inflammatory resolvins. Systematic review evidence confirms omega-3 EPA+DHA supplementation produces significant chronic pain reduction (SMD −0.55).

Eucalyptus inhalation reduced pain severity and improved quality of life in a clinical RCT in rheumatoid arthritis patients experiencing chronic pain. Mechanistically, 1,8-cineole suppresses prostaglandin and cytokine pathways central to chronic pain sensitization. Animal models corroborate antinociceptive and anti-edema effects.

Feverfew (Tanacetum parthenium) contains parthenolide, which inhibits NF-κB and platelet aggregation. Multiple RCTs and the American Headache Society guidelines recognize it for migraine prophylaxis, with studies showing 40–50% reduction in attack frequency. The NIH reports evidence for migraine prevention.

Fish oil provides EPA and DHA omega-3 fatty acids that reduce pro-inflammatory eicosanoid synthesis and generate pro-resolving mediators. A 2025 systematic review/meta-analysis found omega-3 supplementation produces a moderate, significant reduction in chronic pain intensity. A clinical study found ~59% of patients with disc disease could replace NSAIDs with fish oil.

C. speciosa has documented antinociceptive (analgesic) activity in preclinical models. Polysaccharide fractions and flavonoid-rich fractions reduced pain responses in acetic acid writhing tests and CFA-induced arthritis models. The pain-relieving mechanism may involve calcium channel modulation and suppression of pro-inflammatory mediators.

Peimine and verticinone, major alkaloids of fritillary, demonstrate analgesic and pain-suppressive properties in cell and animal models. The MDPI systematic review of FTB identifies pain suppression as one of thirteen documented pharmacological effects. Peimine inhibits MAPK activation in arthritic synoviocytes, a relevant chronic pain mechanism.

Geniposide has documented analgesic properties, and GFE dose-dependently inhibited acetic acid-induced abdominal writhing in mice—a standard preclinical pain model. Genipin is a specific hydroxyl radical scavenger with both analgesic and anti-inflammatory activities. Analgesic/antipyretic use is recognized in the Chinese, Japanese, and Korean Pharmacopeias.

Gentiana macrophylla and its constituent gentiopicroside exhibit significant antinociceptive (pain-reducing) activity in animal models. Analgesic effects have been attributed to downregulation of NR2B (GluN2B) receptor expression in pain pathways. In comparative studies, the extract showed potent antinociceptive activity alongside its anti-inflammatory effects.

Geranium EO aromatherapy has been evaluated in a clinical trial for pain reduction in lumbar spinal stenosis patients with moderate-to-severe pain. Post-herpetic neuralgia is also a documented indication. The oil reduces pain perception via CNS and anti-inflammatory pathways.

Ginger (Zingiber officinale) inhibits prostaglandin synthesis via COX and LOX pathways and acts as a TRPV1 agonist. A 2014 Cochrane review cited ginger among herbs with modest OA pain benefits. Multiple RCTs support its use for osteoarthritis, chronic low-back pain, dysmenorrhea, and migraine, with moderate-to-high quality evidence.

G. littoralis has documented traditional use as an analgesic in TCM, Japanese, and Korean medicine. Published preclinical studies have identified analgesic components in the root and confirmed analgesic properties in the 2019 PMC systematic review. In vitro and animal data support the mechanism.

Glucosamine is a cartilage-building amino sugar studied extensively for osteoarthritis-related chronic joint pain. Evidence is mixed: some large RCTs show benefit for moderate-to-severe OA pain; others show no benefit over placebo for mild OA. NCCIH reports results as unclear, while some guidelines conditionally recommend glucosamine sulfate.

Glycosaminoglycans (GAGs), including chondroitin sulfate, hyaluronic acid, and heparan sulfate, are structural components of cartilage and synovial fluid with established roles in osteoarthritis chronic pain management. Supplementation with GAG-rich preparations from bovine or marine sources reduces joint pain in OA. Traditional use includes cartilage-rich foods in multiple cultures.

Green-lipped mussel (Perna canaliculus) from New Zealand provides a unique profile of omega-3 fatty acids (including ETA) and glycosaminoglycans with anti-inflammatory analgesic effects. RCTs in osteoarthritis and rheumatoid arthritis show significant reductions in joint pain and stiffness. Traditional Māori coastal populations had lower arthritis rates, historically attributed to dietary mussel consumption.

Harpagoside is the principal bioactive iridoid glycoside from Devil's Claw (Harpagophytum procumbens). Cochrane evidence from two high-quality RCTs confirms it reduces chronic low-back pain more than placebo at 50–100 mg/day, with equivalence to 12.5 mg rofecoxib. It inhibits COX and lipoxygenase inflammatory pathways.

Analgesic activity of H. spicatum rhizome extracts has been demonstrated in preclinical models including hot plate, tail flick, and acetic acid writhing tests in rats. The PMC 2012 study confirmed analgesic effects at 200 mg/kg. Essential oils showed antinociception of 33–42% compared to ibuprofen's 43%. The plant is classified in Ayurveda as 'Vedansthapana' (pain reliever).

Linalool, the dominant constituent of ho wood, has demonstrated antinociceptive effects in multiple rodent pain models including inflammatory and neuropathic pain, with effects mediated via opioid and cholinergic pathways.

Hyaluronic acid (HA) is a major component of synovial fluid providing joint lubrication and cushioning. Intra-articular HA injections are established for chronic osteoarthritis knee pain. Oral HA supplementation has emerging evidence for reducing OA joint pain and stiffness, with some RCTs showing benefit.

Impatiens species demonstrate antinociceptive (analgesic) activity in rodent models. Imam et al. (J. Ethnopharmacol., 2012) documented antinociceptive activity of I. balsamina flower methanol extract. I. rothii root extract showed significant analgesic activity at all tested doses in hot plate and acetic acid-induced writhing tests in mice.

Boswellia serrata demonstrates analgesic and anti-inflammatory effects across multiple clinical pain conditions. RCTs in osteoarthritis confirm significant reductions in pain scores, and a 2025 RCT in spondylitis (spinal inflammatory pain) confirmed pain and stiffness reductions. Mechanistically, inhibition of 5-LOX, COX-2, and PGE2 synthesis collectively accounts for the analgesic action.

Several clinical trials have found ipriflavone to have an analgesic adjuvant effect in osteoporosis-related vertebral pain. A 2002 RCT (Rahman et al.) in 32 women with recent osteoporotic vertebral crush fractures found pain at rest and on pressure, as well as supplementary analgesic use, were significantly lower in the ipriflavone group versus placebo after 3 months. A multicenter double-blind 2-year trial in elderly osteoporotic women also documented rapid pain decreases and reduced analgesic intake in the IP group.

Krill oil provides phospholipid-bound EPA and DHA omega-3 fatty acids with superior bioavailability compared to fish oil triglycerides, plus astaxanthin. Clinical trials show krill oil reduces chronic low-back pain and OA joint pain. Phospholipid omega-3s reduce inflammatory markers (CRP, IL-6) relevant to chronic pain.

Lavender essential oil has analgesic and anxiolytic properties via GABAergic and TRPA1/TRPV1 receptor modulation. A 2016 Cochrane review of 14 RCTs (2,050 participants) cited lavender essential oil as reducing pain more than placebo for low-back pain. It is also used traditionally in European herbal medicine for headache and musculoskeletal pain.

Luteolin demonstrates analgesic effects in preclinical models of neuropathic and inflammatory chronic pain. It reduces thermal hyperalgesia, mechanical allodynia, and pain behaviors in multiple animal pain models, and acts synergistically with standard analgesics in the PEA+luteolin combination.

Magnesium deficiency is linked to chronic migraine and musculoskeletal pain. Accumulated evidence from RCTs, case-control, and observational studies shows magnesium supplementation alleviates migraine frequency and severity. It modulates NMDA receptor activity, reducing central sensitization relevant to chronic pain.

Melatonin has antinociceptive and anti-inflammatory properties relevant to chronic pain, particularly fibromyalgia and migraine. Clinical trials show melatonin reduces pain and improves sleep in fibromyalgia. It modulates opioid, GABA, and 5-HT receptors and is listed among supplements with the best evidence for fibromyalgia chronic pain management.

Topical menthol has been evaluated in multiple clinical trials for chronic and neuropathic pain conditions, demonstrating analgesic effects via TRPM8 activation and voltage-gated sodium channel inhibition. Evidence supports its use for musculoskeletal and neuropathic chronic pain.

Methylcobalamin (MeCbl) has documented analgesic effects in several clinical contexts, including diabetic neuropathic pain, herpetic neuralgia, and low back pain. It promotes nerve regeneration and reduces peripheral sensitization via NF-κB modulation. Multiple randomized controlled trials and a meta-analysis support its use, though evidence quality is variable.

M. officinalis iridoid glycosides and M. citrifolia fruit extract demonstrate analgesic activity in preclinical pain models (acetic acid writhing test, hot plate test). In Caribbean traditional medicine, M. citrifolia is referred to as the 'painkiller bush.' Antinociceptive effects of M. officinalis are listed in pharmacological literature.

MSM (methylsulfonylmethane) is an organosulfur compound with anti-inflammatory and antioxidant properties used for osteoarthritis and musculoskeletal chronic pain. The NCCIH acknowledges it among substances used for OA. Some clinical trials show modest pain reduction in knee OA, though a 2011 meta-analysis showed mixed results.

Multiple small clinical trials support CMO's analgesic effects in chronic musculoskeletal pain conditions including knee osteoarthritis and low back pain. A study on axial discogenic low back pain (n=27) found significant reductions in ODI and numeric pain scores after four weeks. A 2002 double-blind RCT of 64 patients with chronic knee pain found significant functional improvement in range of motion. Evidence quality is moderate with small sample sizes.

Myrrh exhibits significant analgesic activity in multiple animal pain models. Furanosesquiterpenes produce local anesthetic effects in nerve cells. A PMC study confirmed myrrh extract's analgesic activity compares favorably to reference analgesics such as diclofenac in rodent models.

Analgesic (antinociceptive) activity of C. rotundus is a well-documented pharmacological property in multiple preclinical models. The sesquiterpene and flavonoid fractions are identified as active analgesic constituents. Traditional use in Ayurveda and TCM for pain conditions is extensive.

OA exhibits analgesic activity in standard animal pain models, including acetic-acid-induced writhing and carrageenan-induced inflammation. Its anti-nociceptive effects are mediated partly through COX inhibition and NF-κB suppression, consistent with its broader anti-inflammatory profile.

Omega-3 fatty acids (EPA and DHA) reduce chronic pain by inhibiting pro-inflammatory prostaglandin E2 and leukotriene B4 synthesis and generating specialized pro-resolving mediators. A 2025 systematic review and meta-analysis (PMC) of multiple RCTs found a moderate, statistically significant reduction in chronic pain intensity (SMD −0.55). Benefits were strongest for rheumatoid arthritis and migraine.

P. foetida demonstrates significant antinociceptive (analgesic) activity in multiple preclinical models covering both central and peripheral pain pathways. Specific iridoid glucosides from the plant show thermal pain inhibition. This is among the most robustly documented pharmacological activities of the plant.

Clinical evidence shows papain reduces post-surgical and post-traumatic pain (RxList cites 1,500 mg/day studied for this purpose). A shingles clinical study of 192 patients found enzyme therapy including papain equivalent to acyclovir for pain and skin lesions. Animal data at 50–100 mg/kg demonstrate analgesic activity via antioxidant and anti-inflammatory pathways.

Feverfew has demonstrated antinociceptive effects in animal models and a direct mechanistic basis through prostaglandin inhibition and NF-κB suppression. It is traditionally promoted for chronic musculoskeletal and inflammatory pain, and its anti-migraine clinical trial data establish a clinical proof-of-concept for pain modulation. One small human RCT found improved grip strength in arthritic pain.

Parthenolide is the principal sesquiterpene lactone bioactive from Feverfew (Tanacetum parthenium), responsible for its analgesic and anti-inflammatory effects. It inhibits NF-κB, platelet aggregation, and prostaglandin synthesis. Studies standardized to ≥0.2% parthenolide content demonstrate migraine prophylactic activity, reducing attack frequency by 40–50% in RCTs.

Palmitoylethanolamide (PEA) is an endogenous fatty acid amide with anti-inflammatory and analgesic properties via PPAR-α activation and endocannabinoid system modulation. A 2023 systematic review and meta-analysis of double-blind RCTs (n=774) found PEA reduces chronic pain with a standardized mean difference of 1.68 points on a standardized 11-point scale (p=0.00001).

Paeoniflorin and TGP have clinically validated analgesic effects relevant to chronic pain, confirmed in animal models via adenosine A1 receptor activation and inflammation inhibition, with clinical evidence from RA and diabetic neuropathy studies.

Systemic proteolytic enzyme therapy has been studied for chronic musculoskeletal pain including neck pain, lumbar osteoarthritis, and post-herpetic neuralgia in clinical trials. A six-week RCT in lumbar OA patients found marked pain reduction with proteolytic enzymes versus NSAIDs. EBSCO Research Starters notes multiple studies found benefit for neck pain, osteoarthritis, and post-herpetic neuralgia, though studies often have methodological limitations.

Piperine, the bioactive alkaloid of black pepper, has direct analgesic and anti-inflammatory properties via TRPV1 desensitization and NF-κB inhibition, and it dramatically enhances bioavailability of curcumin (by ~2,000%). Clinical trials combining piperine with turmeric for chronic pain show enhanced analgesic outcomes. Traditional Ayurvedic medicine uses black pepper to potentiate pain-relieving herbs.

Gall extracts of P. integerrima showed highly significant antinociceptive and analgesic activity (p<0.0001) in mice using acetic acid-induced abdominal constriction, formalin-induced paw licking, and thermally induced pain models, outperforming leaf extracts. Mechanisms involve COX inhibition and opioid receptor interactions.

Opium poppy (Papaver somniferum) is the botanical source of morphine and codeine, the world's benchmark opioid analgesics for moderate-to-severe pain. Their analgesic mechanism via μ-opioid receptor agonism is among the most thoroughly studied pharmacological actions in medicine. This applies to pharmaceutical-grade derivatives, not raw plant preparations.

A randomized, double-blind, placebo-controlled trial (n=94 veterans, JAMA Network Open 2020) demonstrated that pregnenolone significantly reduced chronic low back pain intensity versus placebo after 4 weeks. Analgesic effects are mediated through GABA-A and NMDA receptor modulation and anti-inflammatory properties.

Multiple preclinical studies demonstrate analgesic effects of Zanthoxylum extracts via inhibition of COX/LOX enzymes and NF-κB/ERK signaling pathways. A 7-day mouse study showed reduced swelling and pain markers at 100 mg/kg. Traditional use across multiple cultures documents prickly ash as an analgesic for chronic conditions. No human RCTs exist.

Pre-clinical analgesic and antinociceptive activity of Filipendula ulmaria has been demonstrated in multiple animal studies using validated pain models. The 2025 Marinov et al. study in Pharmacia is the most recent, showing dose-dependent antinociceptive effects. The salicylate-based mechanism provides direct pharmacological rationale.

Quercetin is a polyphenolic flavonoid with anti-inflammatory and antioxidant properties that reduce chronic pain-related inflammation. It inhibits NF-κB, COX-2, and lipoxygenase pathways and reduces histamine-mediated pain sensitization. Evidence supports its role in reducing inflammation associated with arthritis and other chronic pain conditions.

Rosehip powder has documented clinical benefits for chronic pain, particularly in arthritis and lower back pain. A meta-analysis of three RCTs (n=287) found patients twice as likely to respond to rosehip versus placebo for arthritic pain. A review confirmed rosehip has 'beneficial effects on osteoarthritis, rheumatoid arthritis and back pain.'

Rose hip (Rosa canina) preparations have been studied for chronic pain, particularly osteoarthritis and rheumatoid arthritis. Multiple RCTs demonstrate significant reductions in OA pain and stiffness. A systematic review of diet and chronic pain classified rose hip as having 'small to medium positive effect on chronic pain based on moderate to high quality evidence.'

Rosemary—both topically and orally—has demonstrated analgesic effects in human clinical trials, including reductions in musculoskeletal pain in hemodialysis patients and joint pain in arthritis patients. Its antinociceptive properties are attributed to COX-2 inhibition, lipoxygenase inhibition, and modulation of pain-related inflammatory mediators.

A 2025 PubMed review described preclinical evidence for rutin's analgesic activity across inflammatory pain and neuropathic pain models, operating via anti-inflammatory and antioxidant pathways. Human clinical trials for pain endpoints have not yet been conducted, placing the current evidence at the preclinical-scientific level.

Salicin is the primary analgesic glycoside in white willow bark (Salix alba), metabolized to salicylic acid in vivo. Clinical trials with 120–240 mg/day standardized salicin reduced chronic low-back pain more than placebo, with 240 mg equivalent to rofecoxib 12.5 mg/day. It provides sustained analgesia with reduced GI risk versus synthetic aspirin.

SAMe (S-adenosylmethionine) is a naturally occurring compound with analgesic and anti-inflammatory properties studied for osteoarthritis chronic pain. The NCCIH identifies it as a treatment option for OA though evidence is unclear. A 2009 Cochrane review of 4 trials (656 participants) comparing SAMe to placebo was inconclusive but suggested potential benefit.

Preclinical rodent studies demonstrate analgesic properties of mesembrine in nociception assays without abuse liability or ataxia. Traditional use as an analgesic and painkiller by San and Khoikhoi peoples is well-documented. No human clinical trial has been conducted for chronic pain as a primary endpoint.

Serratiopeptidase has been clinically used for chronic pain across multiple specialties including orthopedics, dentistry, and otolaryngology. Its analgesic mechanism involves hydrolysis of bradykinin, histamine, and serotonin—pain-signaling mediators. While multiple RCTs show anti-inflammatory and anti-edemic benefits, the analgesic evidence specifically is less robust, with the 2013 Bhagat systematic review noting insufficient evidence for pure analgesic efficacy.

Hydroxy-α-sanshool and other alkylamides from Z. bungeanum act on TRPV1/TRPA1 channels and KCNK two-pore domain potassium channels to produce analgesic and local anesthetic effects. Animal pain models (writhing, formalin, hot-plate) consistently show reduced pain responses. TCM has used Sichuan pepper topically and internally for pain for over 2,000 years.

SD's analgesic and anti-hyperalgesic properties have been documented in preclinical animal pain models, with coumarin anomalin specifically shown to inhibit NF-κB, MAPKs, and CREB signaling in both acute and chronic inflammatory pain models in mice. Chromone glucosides also have documented analgesic pharmacodynamics. All evidence is preclinical.

Analgesic properties have been identified for A. julibrissin in preclinical research. Anti-inflammatory activity and TCM use for traumatic pain and rheumatic discomfort support its relevance to chronic pain contexts.

A. muricata fruit and leaf extracts demonstrate dose-dependent analgesic and anti-inflammatory activity in multiple validated rodent pain models. The analgesic mechanism is partially opioid-mediated. Traditional use for neuralgia, rheumatism, and arthritic pain further supports this link.

Analgesic activity is among the pharmacologically confirmed properties of S. indicus across multiple preclinical studies, including protection from acetic acid-induced writhing in rodents. Traditional use for pectoralgia and other pain conditions supports this profile.

A human clinical trial of an SPM-enriched marine lipid fraction demonstrated significant reductions in pain intensity, pain interference, and quality of life in adults with chronic pain. Preclinical evidence spanning inflammatory, post-operative, and neuropathic pain models is extensive. Spinal cord stimulation increases cerebrospinal fluid RvD1 in humans.

SJW has been tested for chronic pain; animal models show antinociceptive effects mediated by hyperforin and hypericin. However, available human RCTs (neuropathy studies) produced negative results. An EBSCO review noted neither of two small human studies provided strong evidence for SJW as a chronic pain treatment.

Alcoholic P. paniculata root extract demonstrated analgesic activity specifically against inflammatory pain in rat models, including inhibition of carrageenan-induced edema and writhing test responses (Mazzanti & Braghiroli, 1994). The analgesic effect was absent for non-inflammatory pain, indicating a mechanism tied to inflammation pathways.

CX has demonstrated analgesic properties in multiple animal pain models (hot plate, writhing test, dysmenorrhea). TMP's analgesic mechanism involves actions at P2X3 receptors on primary afferent neurons. TCM uses CX widely for pain due to blood stasis and qi stagnation across musculoskeletal, gynecological, and headache contexts.

Preclinical studies have confirmed analgesic and anti-nociceptive activity of Dipsacus asper extracts in animal models. The herb is classified in TCM and Korean Medicine as an analgesic for chronic musculoskeletal pain. Asperosaponin VI has been identified as having analgesic properties in pharmacological reviews.

A 12-week open-label clinical case series evaluated 150 mg n-enriched THIAA combined with undenatured type II collagen in patients with chronic joint pain from OA and RA. THIAA's inhibition of COX-2, NF-κB, and PGE2 pathways underpins a plausible mechanism for pain modulation. Evidence is preliminary, limited to a single small open-label study.

Tetrahydropalmatine (THP), the primary analgesic alkaloid from Corydalis yanhusuo, antagonizes dopamine D1/D2 receptors and partially agonizes opioid receptors to produce analgesia. Clinical studies have confirmed its effects in neuralgia, dysmenorrhea, and headache. Animal studies confirm antihyperalgesic activity in chronic inflammatory and neuropathic pain models.

Oral trypsin-containing enzyme combinations have demonstrated analgesic effects in clinical trials across multiple pain conditions including osteoarthritis and post-surgical pain. Equivalence to NSAIDs in knee OA pain trials is the strongest evidence. Trypsin:chymotrypsin also shows analgesic properties in maxillofacial and orthopedic surgical recovery.

Turmeric root (Curcuma longa) contains curcuminoids that reduce chronic pain through NF-κB and COX-2 inhibition. A randomized crossover clinical trial in adults with moderate chronic pain confirmed analgesic effects at dietary doses. A 2014 Cochrane review cited ginger and Boswellia alongside turmeric-derived compounds for OA benefit.

Vitamin D deficiency is significantly associated with chronic musculoskeletal pain and fibromyalgia. A systematic review of 14 RCTs found that vitamin D supplementation reduces pain in deficient patients. It modulates inflammatory cytokines (TNF-α, IL-17) and suppresses central sensitization pathways relevant to chronic pain.

Vitamin D3 (cholecalciferol) is the most bioavailable and clinically studied form of vitamin D for chronic pain. RCTs show supplementation reduces pain in deficient individuals with fibromyalgia and chronic musculoskeletal pain. It suppresses neuroinflammatory cytokines TNF-α, IL-17 and modulates central pain sensitization.

White willow bark (Salix alba) contains salicin, which is metabolized to salicylic acid in vivo. A Cochrane review found daily doses of 120–240 mg salicin moderately better than placebo for chronic low-back pain, with 240 mg equivalent to rofecoxib 12.5 mg/day. Its analgesic tradition dates to ancient Egyptian and Greek medicine.

Willow bark extract has demonstrated efficacy for chronic pain specifically in the setting of low back pain exacerbations (RCT, n=191, dose-dependent response) and in musculoskeletal pain broadly. A 2009 systematic review covering four RCTs concluded moderate evidence of effectiveness. The EMA formally recognizes willow bark for short-term treatment of lower back pain, one of the most common chronic pain conditions. Its analgesic mechanism—COX inhibition, prostaglandin suppression, and NF-κB blockade—is relevant across chronic pain states.

Topical methyl salicylate preparations have been evaluated in systematic reviews for both acute and chronic pain. A Cochrane-level systematic review found evidence of benefit for acute pain but weaker evidence for chronic musculoskeletal pain. A large Phase IV trial (n=3,515) demonstrated significant VAS reduction in subjects with chronic soft tissue pain using compound methyl salicylate liniment.

Yucca's saponins and polyphenolics are documented to produce anti-inflammatory and anti-spasmodic effects that reduce pain associated with arthritis. The Bingham (1975) double-blind trial demonstrated pain relief in arthritic patients. ScienceDirect's overview of Yucca schidigera specifically states the plant 'produce[s] anti-inflammatory, antioxidant, and anti-spasmodic effects to reduce pain associated with arthritis.' Evidence applies primarily to inflammatory joint pain rather than neuropathic or general chronic pain.

Antinociceptive and analgesic properties of Zanthoxylum are supported by multiple preclinical studies. Z. nitidum extract suppressed CFA-induced chronic inflammatory pain in mice via ERK1/2 and NF-κB signaling inhibition. The genus' use for chronic pain (rheumatism, arthralgia, injuries) is also extensively documented in TCM and global traditional medicine.

Amber has been used across European and Asian traditional medicine as a natural analgesic for chronic pain, including joint and muscle pain. Bioactive terpenes and succinic acid are proposed mediators. Worn amber jewelry for pain relief lacks clinical evidence, but oral/tincture use has a documented folk history.

Black cohosh has a long ethnobotanical record as a pain-relieving herb used by Native Americans and eclectic physicians for musculoskeletal and neuralgic pain. Recent mechanistic research implicates μ-opioid receptor partial agonism as a plausible antinociceptive pathway, though no RCTs have used chronic pain as a primary endpoint.

Cajuput oil is a documented analgesic across Southeast Asian and Ayurvedic traditional medicine, used topically for chronic pain conditions including neuralgia, rheumatism, and back pain. Its pharmacological mechanism as a counter-irritant (1,8-cineole) and smooth-muscle relaxant supports this use. It is an ingredient in Tiger Balm and commercial pain-relief preparations. No human RCTs specific to cajuput for chronic pain exist.

Jamaican dogwood is the primary dogwood species with a documented traditional use for chronic pain, serving as an analgesic and sedative for various painful conditions including nerve pain, rheumatic pain, and muscle spasm. Animal data confirm analgesic activity. No human clinical trials exist.

Gastrodin is described as an analgesic in pharmacological reviews and has been used in TCM for limb pain, numbness, and neuralgia. Classical texts and Pharmacopoeia preparations reference pain-related indications. Dedicated human RCTs for chronic pain are not available.

Kanna has a documented ethnobotanical record as a painkiller used by San and Khoikhoi peoples for pain relief, including musculoskeletal pain (hunters washing aching legs with kanna preparations). Preclinical evidence suggests opioid receptor activation. No human clinical trials have assessed kanna for chronic pain.

Kava's kavalactones produce analgesic effects through non-opiate mechanisms including COX inhibition and voltage-gated ion channel blockade, demonstrated in preclinical models. Traditional Pacific medicine uses kava for various chronic pain states. Some preliminary clinical data on kava for anxiety-associated pain exist, but no dedicated human RCT for chronic pain has been conducted.

Eclectic physicians considered lobelia a useful pain reliever, using it both internally and in topical liniments for neuralgic, rheumatic, and chronic pain syndromes. PeaceHealth (citing King's American Dispensatory) documents it as "a useful pain reliever." No clinical trials have evaluated this use.

Practitioners in traditional Chinese and Native American medicine use skullcap to treat chronic pain including neuralgia and musculoskeletal pain. Preclinical evidence shows baicalein reduces neuropathic pain. The antispasmodic and anti-inflammatory properties of skullcap support multiple chronic pain mechanisms.

Spruce resin plasters and bark decoctions have traditional use for chronic pain in rheumatism and musculoskeletal conditions. Sitka spruce cone decoctions were taken for pain relief. Spruce needle oil bath preparations carry European traditional use for pain. Anti-inflammatory and analgesic terpene constituents provide biochemical plausibility.

Wild yam's traditional use for pain spans arthritis, neuralgia, colic, and menstrual cramps. A preclinical study (Lima et al., BMC CAM 2013) confirmed antinociceptive effects of D. villosa extract in rodent pain models. No controlled human clinical trials for chronic pain have been conducted.