REVIEW PAPER
Genetic aspects of pain and its variability in the human population
 
More details
Hide details
1
Department of Anaesthesiology and Intensive Care, University Hospital, Collegium Medicum, University of Zielona Góra, Poland
 
2
Department of Neurology, University Hospital, Zielona Góra, Collegium Medicum, University of Zielona Góra, Poland
 
3
Faculty of Social Medicine, Medical University, Łódź, Poland
 
 
Corresponding author
Wojciech Wiesław Świtała   

Department of Anaesthesiology and Intensive Care, University Hospital Zielona Góra Collegium Medicum, University of Zielona Góra, Poland, Zyty 26, 65-001, Zielona Góra, Poland
 
 
Ann Agric Environ Med. 2021;28(4):569-574
 
KEYWORDS
TOPICS
ABSTRACT
The sensation of pain is common to both animals and human beings. Its threshold, intensity, tolerability, and characteristics are variable and depend on ethnicity, gender, stress exposure, co-existing mental disorders, such as depression or anxiety, social and economical background, as well as on genetic factors. It is estimated that about 5 and 20 percent of population suffer from acute and chronic pain, respectively, which results in the search for medical advice in healthcare facilities, and causes great expenses in health care budgets worldwide. Research aimed at identifying the causative agents of pain syndromes include single nucleotidepolymorphism (SNP), family history studies, twin siblings’ genetic diversity studies, and recently, also a genome-wide association study (GWAS). Clinical syndromes of derangement of pain sensation are generally caused by single gene mutations (e.g. erythromelalgia and paroxysmal extreme pain disorder caused by mutations of SCN9A), but can also be associated with multiple gene mutations, as happens in migraine, fibromyalgia or hereditary sensory and autonomic neuropathies. Structural changes of proteins caused by gene mutations involve various cellular element, such as ion channels, receptors, scaffolding proteins, enzymes, transporting proteins, eventually leading to numerous clinical entities in which pain or its lack remain the leading symptoms. The sensation of pain is initiated by a stimulus, which activates the free nerve endings via chemical mediators, and the mechanical stimuli is then transmitted to the brain along the neurons and spinal tracts. Synaptic neurotransmitters and cell structures take part in this process and eventually affect the intensity of pain sensation.
 
REFERENCES (40)
1.
Beckman L. The neural basis of behavior. Springer; 2012. p. 311–334.
 
2.
Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain. 2006; 10(4): 287–287. Available from: http://doi.wiley.com/10.1016/j... [cited 2020 Oct 30].
 
3.
Pitcher M, Von Korff M, Bushnell MC, Porter L. Prevalence and Profile of High Impact Chronic Pain in the United States. Pain. 2019; 20(2): 146–160.
 
4.
Śliwiński Z, Starczyńska M, Śliwa M, Kiebzak W. Quality of life in patients with lumbar spinal pain. Fizjoterapia Pol. 2014; 14(2): 26–39.
 
5.
Wiesenfeld-Hallin Z. Sex differences in pain perception. Gend Med. 2005; 2: 137–45. Available from: https://pubmed.ncbi.nlm.nih.go... [cited 2020 Oct 30].
 
6.
Sharma M, Kantorovich S, Lee C, Anand N, Blanchard J, Fung ET, Meshkin B, Brenton A, Richeimer S. An observational study of the impact of genetic testing for pain perception in the clinical management of chronic non-cancer pain. J Psychiatr Res. 2017; 89: 65–72.
 
7.
Webster LR, Belfer I. Pharmacogenetics and Personalized Medicine in Pain Management. Clin Lab Med. 2016 Sep; 36(3): 493–506.
 
8.
Capsoni S. From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V. Eur J Neurosci. 2014; 39(3): 392–400.
 
9.
Manganelli F, Parisi S, Nolano M, et al. Novel mutations in dystonin provide clues to the pathomechanisms of HSAN-VI. Neurology 2017; 88(22): 2132–2140.
 
10.
Wilson ER, Kugathasan U, Abramov AY, et al. Hereditary sensory neuropathy type 1-associated deoxysphingolipids cause neurotoxicity, acute calcium handling abnormalities and mitochondrial dysfunction in vitro. Neurobiol Dis. 2018: 1–14.
 
11.
Lötsch J, Doehring A, Mogil JS, Arndt T, Geisslinger G, Ultsch A. Functional genomics of pain in analgesic drug development and therapy. Pharmacol Ther. 2013; 139(1): 60–70.
 
12.
Axelrod FB, Kaufmann H. Hereditary Sensory and Autonomic Neuropathies. Neuromuscular Disorders of Infancy, Childhood, and Adolescence. 2nd ed. A Clinician’s Approach; 2015. p. 340–352.
 
13.
Woods CG, Babiker MOE, Horrocks I, Tolmie J, Kurth I. The phenotype of congenital insensitivity to pain due to the NaV1. 9 variant p. L811P. Eur J Hum Genet. 2015; 23: 561.
 
14.
Phatarakijnirund V, Mumm S, McAlister WH, Novack DV, Wenkert D, Clements KL, Whyte MP. Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9. Bone 2016; 84: 289–98.
 
15.
Chen YC, Auer-Grumbach M, et al. Transcriptional regulator PRDM12 is essential for human pain perception. Nat Genet. 2015; 47: 803–8.
 
16.
Schmidt-Wilcke T, Diers M. New Insights into the Pathophysiology and Treatment of Fibromyalgia. Biomedicines 2017; 5(2): 22.
 
17.
The International Classification of Headache Disorders. 3rd ed. Cephalalgia. 2013; 33: 629–808.
 
18.
Charles A. The pathophysiology of migraine: implications for clinical management. The Lancet Neurol. 2018; 17(2): 174–182.
 
19.
Tabak J, Kopański Z, Kulesza-Mrowiecka M, et al. Headaches-selected epidemiological aspects and etiopatogenesis. J Clin Healthcare. 2018; 2: 23–27.
 
20.
Sipahi T, Guldiken B, Kabayel L, Palabiyik O, Ozkan H, Kilic TO, Sut N, Turgut N. Endothelial Nitric Oxide Synthase and Angiotensin Converting Enzyme Gene Polymorphisms in Migraine Patients. Noro Psikiyatr Ars. 2013; 50(3): 274–278.
 
21.
Fan Ch, Wolking S, et al. Early-onset familial hemiplegic migraine due to a novel SCN1A mutation. Cephalalgia. 2016; 36(13): 1238–1247.
 
22.
Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache: J Head Face Pain. 2015; (2).
 
23.
Akopian AN. Approaches to Cloning of Pain-Related Ion Channel Genes. Methods Mol Biol. 2013; 998: 3–19.
 
24.
Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostics criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010; 62(5): 600–610.
 
25.
Eich W, Bar KJ, et al. Definition, Klassifikation klinische Diagnose und Prognose des Fibromyalgiesyndroms: Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten; Schmerz. 2017; 31(3): 231–238.
 
26.
Fillingim RB, Smith SB, Maixner W. The phenotypic and genetic signatures of common musculoskeletal pain conditions. Nat Rev Rheumatol. 2013; 9(6): 340–50. doi: 10.1038/nrrheum.2013.43. Epub 2013 Apr 2.
 
27.
Martí TM, Llordés ML, Jorda MC, et al. Profile of patients with fibromyalgia being treated in primary care centers in Terrassa, a city in northeastern Spain. Reumatol Clin. 2017; 13(5): 252–257.
 
28.
Anderson RJ, McCrae CS, Staud R, et al. Predictors of clinical pain in fibromyalgia: examining the role of sleep. J Pain 2012; 13(4): 350–358.
 
29.
Dolcino M, Tinazzi E, Puccetti A, Lunardi C. Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy. J Clin Med. 2020; 9(6): 1814. doi: 10.3390/jcm9061814. PMID: 32532082; PMCID: PMC7356177.
 
30.
Rusu AC, Scholich S, Meloto CB, Diatchenko L. Subgrouping of Low Back Pain Patients for Targeting Treatments Evidence from Genetic, Psychological, and Activity-related Behavioral Approaches. Clin J Pain. 2015; 31(2): 123–32.
 
31.
Sumpton JE, Moulin DE. Fibromyalgia, neurotransmitter, pathophysiology. Handb Clin Neurol. 2014; 119: 513–527.
 
32.
Wolfe F, Cloudw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec; 46(3).
 
33.
Kleggetveit IP, Schmidt R, Namer B, Salter H, Helas T, Schmelz M, Jorum E . Pathological nociceptors in two patients with erythromelalgia-like symptoms and rare genetic Nav 1.9 variants. Brain Behav. 2016; 6(10).
 
34.
Emery EC, Habib AM, Cox JJ, et al. Novel SCN9A mutations underlying extreme pain phenotypes: unexpected electrophysiological and clinical phenotype correlations. J Neurosci. 2015; 35: 7674–81.
 
35.
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian VA, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurol. 2016; 73(6): 659–667.
 
36.
Sablonniere B, Huin V, Cuvellier J, Genet A, Dhaenens C, Vallee L. A Novel SCN9A gene Mutation in a Patient with Carbamazepine-Resistant Paroxysmal Extreme Pain Disorder. J Pediatric Neurol Dis. 2015; 1: 104. doi: 10.4172/2572-5203.1000104.
 
37.
Todorovic M, Haroutounian S, Dworkin R, Freeman R. Diagnostic Criteria for Idiopathic Small Fiber Neuropathy – A Systematic Literature Review. J Pain. 2019; 20(4): S118.
 
38.
Han C, Yang Y, de Greef BT, Hoeijmakers JG, Gerrits MM, Verhamme C, Qu J, Lauria G, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. The domain II S4-S5 linker in Nav1.9: a missense mutation enhances activation, impairs fast inactivation, and produces human painful neuropathy. Neuromolecular Med. 2015; 17: 158–69.
 
39.
Leng XR, Qi XH, Zhou YT, Wang YP. Gain-of-function mutation p. Arg225Cys in SCN11A causes familial episodic pain and contributes to essential tremor. J Hum Genet. 2017; 62: 641–6.
 
40.
Bennett DL, Woods CG. Painful and painless channelopathies. Lancet Neurol. 2014; 13(6): 587–99.
 
eISSN:1898-2263
ISSN:1232-1966
Journals System - logo
Scroll to top