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MedGen UID:
Concept ID:
Sign or Symptom
Synonyms: Dolor; Pain observations; Painful; Part hurts
SNOMED CT: Pain observations (22253000); Pain (22253000); Dolor (22253000); Painful (22253000); Part hurts (22253000)
HPO: HP:0012531


An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Pain

Conditions with this feature

Primary erythromelalgia
MedGen UID:
Concept ID:
Disease or Syndrome
SCN9A neuropathic pain syndromes (SCN9A-NPS) comprise SCN9A erythromelalgia (EM), SCN9A paroxysmal extreme pain disorder (PEPD), and SCN9A small fiber neuropathy (SFN). SCN9A-EM is characterized by recurrent episodes of bilateral intense, burning pain, and redness, warmth, and occasionally swelling. While the feet are more commonly affected than the hands, in severely affected individuals the legs, arms, face, and/or ears may be involved. SCN9A-PEPD is characterized by neonatal or infantile onset of autonomic manifestations that can include skin flushing, harlequin (patchy or asymmetric) color change, tonic non-epileptic attacks (stiffening), and syncope with bradycardia. Later manifestations are episodes of excruciating deep burning rectal, ocular, or submandibular pain accompanied by flushing (erythematous skin changes). SCN9A-SFN is characterized by adult-onset neuropathic pain in a stocking and glove distribution, often with a burning quality; autonomic manifestations such as dry eyes, mouth, orthostatic dizziness, palpitations, bowel or bladder disturbances; and preservation of large nerve fiber functions (normal strength, tendon reflexes, and vibration sense).
Thromboangiitis obliterans
MedGen UID:
Concept ID:
Disease or Syndrome
A rare inflammatory, non-necrotizing, non-atherosclerotic, occlusive vascular disease characterized by thrombosis and recanalization affecting small and medium sized arteries and veins of upper and lower extremities.
Cluster headache, familial
MedGen UID:
Concept ID:
Disease or Syndrome
The Headache Classification Committee of the International Headache Society (1988) listed the following criteria for cluster headache (CH): at least 5 attacks of severe unilateral orbital, supraorbital, and/or temporal pain, lasting 15 to 180 minutes, associated with at least 1 of 8 local autonomic signs, and occurring once every other day to 8 per day. Approximately 85% of CH patients have the episodic subtype, in which the headaches occur in cluster periods lasting from 7 days to 1 year and separated by attack-free intervals of 1 month or more. The remainder of patients have the chronic subtype, in which attacks recur for greater than 1 year without remission or with remissions lasting less than 1 month (Lipton et al., 2004).
Leukocyte adhesion deficiency 3
MedGen UID:
Concept ID:
Disease or Syndrome
Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is an autosomal recessive disorder characterized by LAD1 (116920)-like immune deficiency and Glanzmann thrombasthenia (GT; 273800)-like bleeding problems. LAD3 results from mutations in FERMT3, or KINDLIN3, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells. In LAD3, the adhesive functions of integrins on both leukocytes and platelets are disrupted, most likely due to defects in activation-dependent alterations of surface integrins that enable high-avidity binding to ligands on target cells, a process termed 'inside-out signaling' (Svensson et al., 2009; Zimmerman, 2009). For a discussion of genetic heterogeneity of leukocyte adhesion deficiency, see 116920.
Familial episodic pain syndrome with predominantly upper body involvement
MedGen UID:
Concept ID:
Disease or Syndrome
Familial episodic pain syndrome-1 is an autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress (summary by Kremeyer et al., 2010). Genetic Heterogeneity of Familial Episodic Pain Syndrome See also FEPS2 (615551), caused by mutation in the SCN10A gene (604427) on chromosome 3p22, and FEPS3 (615552), caused by mutation in the SCN11A gene (604385) on chromosome 3p22.
Familial episodic pain syndrome with predominantly lower limb involvement
MedGen UID:
Concept ID:
Disease or Syndrome
Familial episodic pain syndrome-3 (FEPS3) is an autosomal dominant disorder characterized by early childhood onset of intense episodic pain mainly affecting the distal lower extremities, but sometimes affecting the upper extremities as well. The pain comes in cycles lasting several days, is exacerbated by fatigue, may be accompanied by sweating, and can be relieved by antiinflammatory medication. Severe episodic pain tends to diminish with age (summary by Zhang et al., 2013). For a discussion of the genetic heterogeneity of familial episodic pain syndrome, see FEPS1 (615040).
Primary coenzyme Q10 deficiency 8
MedGen UID:
Concept ID:
Disease or Syndrome
Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen.
Charcot-Marie-Tooth disease type 2A2
MedGen UID:
Concept ID:
Disease or Syndrome
MFN2 hereditary motor and sensory neuropathy (MFN2-HMSN) is a classic axonal peripheral sensorimotor neuropathy, inherited in either an autosomal dominant (AD) manner (~90%) or an autosomal recessive (AR) manner (~10%). MFN2-HMSN is characterized by more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Median onset is age 12 years in the AD form and age eight years in the AR form. The prevalence of optic atrophy is approximately 7% in the AD form and approximately 20% in the AR form.
Congenital disorder of deglycosylation 1
MedGen UID:
Concept ID:
Disease or Syndrome
Individuals with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) typically display a clinical tetrad of developmental delay / intellectual disability in the mild to profound range, hypo- or alacrima, elevated liver transaminases that may spontaneously resolve in childhood, and a complex hyperkinetic movement disorder that can include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. About half of affected individuals will develop clinical seizures. Other findings may include obstructive and/or central sleep apnea, oral motor defects that affect feeding ability, auditory neuropathy, constipation, scoliosis, and peripheral neuropathy.

Professional guidelines


Gibbs D, McGahan BG, Ropper AE, Xu DS
Neurol Clin 2023 Feb;41(1):61-76. Epub 2022 Oct 29 doi: 10.1016/j.ncl.2022.07.002. PMID: 36400559
Vuurberg G, Hoorntje A, Wink LM, van der Doelen BFW, van den Bekerom MP, Dekker R, van Dijk CN, Krips R, Loogman MCM, Ridderikhof ML, Smithuis FF, Stufkens SAS, Verhagen EALM, de Bie RA, Kerkhoffs GMMJ
Br J Sports Med 2018 Aug;52(15):956. Epub 2018 Mar 7 doi: 10.1136/bjsports-2017-098106. PMID: 29514819
Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L; American College of Gastroenterology
Am J Gastroenterol 2013 Jan;108(1):18-37; quiz 38. Epub 2012 Nov 13 doi: 10.1038/ajg.2012.373. PMID: 23147521Free PMC Article

Recent clinical studies


Zieliński J, Morawska-Kochman M, Zatoński T
Adv Clin Exp Med 2020 Mar;29(3):365-374. doi: 10.17219/acem/112600. PMID: 32129952
Kelly RB, Willis J
Am Fam Physician 2019 Jul 15;100(2):89-96. PMID: 31305037
Violante FS, Mattioli S, Bonfiglioli R
Handb Clin Neurol 2015;131:397-410. doi: 10.1016/B978-0-444-62627-1.00020-2. PMID: 26563799
Cartwright SL, Knudson MP
Am Fam Physician 2008 Apr 1;77(7):971-8. PMID: 18441863
Haefeli M, Elfering A
Eur Spine J 2006 Jan;15 Suppl 1(Suppl 1):S17-24. Epub 2005 Dec 1 doi: 10.1007/s00586-005-1044-x. PMID: 16320034Free PMC Article


Willy RW, Hoglund LT, Barton CJ, Bolgla LA, Scalzitti DA, Logerstedt DS, Lynch AD, Snyder-Mackler L, McDonough CM
J Orthop Sports Phys Ther 2019 Sep;49(9):CPG1-CPG95. doi: 10.2519/jospt.2019.0302. PMID: 31475628
Urits I, Burshtein A, Sharma M, Testa L, Gold PA, Orhurhu V, Viswanath O, Jones MR, Sidransky MA, Spektor B, Kaye AD
Curr Pain Headache Rep 2019 Mar 11;23(3):23. doi: 10.1007/s11916-019-0757-1. PMID: 30854609
Meints SM, Edwards RR
Prog Neuropsychopharmacol Biol Psychiatry 2018 Dec 20;87(Pt B):168-182. Epub 2018 Jan 31 doi: 10.1016/j.pnpbp.2018.01.017. PMID: 29408484Free PMC Article
Violante FS, Mattioli S, Bonfiglioli R
Handb Clin Neurol 2015;131:397-410. doi: 10.1016/B978-0-444-62627-1.00020-2. PMID: 26563799
Cartwright SL, Knudson MP
Am Fam Physician 2008 Apr 1;77(7):971-8. PMID: 18441863


Lim CY, In J
Korean J Anesthesiol 2019 Jun;72(3):221-232. Epub 2019 Apr 1 doi: 10.4097/kja.19049. PMID: 30929415Free PMC Article
Dworkin RH, Turk DC, Peirce-Sandner S, Baron R, Bellamy N, Burke LB, Chappell A, Chartier K, Cleeland CS, Costello A, Cowan P, Dimitrova R, Ellenberg S, Farrar JT, French JA, Gilron I, Hertz S, Jadad AR, Jay GW, Kalliomäki J, Katz NP, Kerns RD, Manning DC, McDermott MP, McGrath PJ, Narayana A, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Reeve BB, Rhodes T, Sampaio C, Simpson DM, Stauffer JW, Stucki G, Tobias J, White RE, Witter J
Pain 2010 May;149(2):177-193. Epub 2010 Mar 6 doi: 10.1016/j.pain.2010.02.018. PMID: 20207481
Manchikanti L, Hirsch JA, Smith HS
Pain Physician 2008 Nov-Dec;11(6):717-73. PMID: 19057624
Johnson CD, Budd J, Ward AJ
Dis Colon Rectum 1987 Oct;30(10):780-1. doi: 10.1007/BF02554626. PMID: 2820672
Bloomfield SS, Mitchell J, Cissell G, Barden TP
Pain 1986 Nov;27(2):171-179. doi: 10.1016/0304-3959(86)90208-3. PMID: 3540812


Burton JK, Craig LE, Yong SQ, Siddiqi N, Teale EA, Woodhouse R, Barugh AJ, Shepherd AM, Brunton A, Freeman SC, Sutton AJ, Quinn TJ
Cochrane Database Syst Rev 2021 Jul 19;7(7):CD013307. doi: 10.1002/14651858.CD013307.pub2. PMID: 34280303Free PMC Article
Safiri S, Kolahi AA, Cross M, Hill C, Smith E, Carson-Chahhoud K, Mansournia MA, Almasi-Hashiani A, Ashrafi-Asgarabad A, Kaufman J, Sepidarkish M, Shakouri SK, Hoy D, Woolf AD, March L, Collins G, Buchbinder R
Arthritis Rheumatol 2021 Apr;73(4):702-714. Epub 2021 Feb 22 doi: 10.1002/art.41571. PMID: 33150702
Mulvad B, Nielsen RO, Lind M, Ramskov D
PLoS One 2018;13(10):e0204742. Epub 2018 Oct 12 doi: 10.1371/journal.pone.0204742. PMID: 30312310Free PMC Article
McGovern MM, Avetisyan R, Sanson BJ, Lidove O
Orphanet J Rare Dis 2017 Feb 23;12(1):41. doi: 10.1186/s13023-017-0572-x. PMID: 28228103Free PMC Article
Gavin NC, Webster J, Chan RJ, Rickard CM
Cochrane Database Syst Rev 2016 Feb 1;2(2):CD009213. doi: 10.1002/14651858.CD009213.pub2. PMID: 26827714Free PMC Article

Clinical prediction guides

Jonsson A, Rasmussen-Barr E
Physiother Theory Pract 2018 Mar;34(3):165-180. Epub 2017 Nov 7 doi: 10.1080/09593985.2017.1390806. PMID: 29111857
Denteneer L, Stassijns G, De Hertogh W, Truijen S, Van Daele U
Arch Phys Med Rehabil 2017 Jan;98(1):151-164.e6. Epub 2016 Aug 26 doi: 10.1016/j.apmr.2016.07.020. PMID: 27568883
Ledowski T, Burke J, Hruby J
Br J Anaesth 2016 Sep;117(3):371-4. doi: 10.1093/bja/aew226. PMID: 27543532
Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR
Paediatr Anaesth 2006 Mar;16(3):258-65. doi: 10.1111/j.1460-9592.2005.01773.x. PMID: 16490089
Sun Y, Stürmer T, Günther KP, Brenner H
Clin Rheumatol 1997 Mar;16(2):185-98. doi: 10.1007/BF02247849. PMID: 9093802

Recent systematic reviews

Hayden JA, Ellis J, Ogilvie R, Stewart SA, Bagg MK, Stanojevic S, Yamato TP, Saragiotto BT
J Physiother 2021 Oct;67(4):252-262. Epub 2021 Sep 16 doi: 10.1016/j.jphys.2021.09.004. PMID: 34538747
Lew J, Kim J, Nair P
J Man Manip Ther 2021 Jun;29(3):136-146. Epub 2020 Sep 22 doi: 10.1080/10669817.2020.1822618. PMID: 32962567Free PMC Article
Miake-Lye IM, Mak S, Lee J, Luger T, Taylor SL, Shanman R, Beroes-Severin JM, Shekelle PG
J Altern Complement Med 2019 May;25(5):475-502. Epub 2019 Mar 20 doi: 10.1089/acm.2018.0282. PMID: 30892910Free PMC Article
Karcioglu O, Topacoglu H, Dikme O, Dikme O
Am J Emerg Med 2018 Apr;36(4):707-714. Epub 2018 Jan 6 doi: 10.1016/j.ajem.2018.01.008. PMID: 29321111
van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, Tjan-Heijnen VC, Janssen DJ
J Pain Symptom Manage 2016 Jun;51(6):1070-1090.e9. Epub 2016 Apr 23 doi: 10.1016/j.jpainsymman.2015.12.340. PMID: 27112310

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