Stress Can Hurt… Literally

A study in the journal Pain (Bortsov 2012) reports genetic variants increase the risk of developing chronic pain following a traumatic event.

The study followed two groups that had undergone traumatic events, motor vehicle collisions and sexual assault. It looked at gene variations encoding FK506 binding protein 51 (FKBP5); a co-chaperone with heat-binding protein 90 (hps90), together they help regulate glucocorticoid receptor sensitivity (Binder 2009) and ultimately influences HPA function.

http://en.wikipedia.org/wiki/Hypothalamic-pituitary-adrenal_axis

Credit: Wikipedia

The hypothalamic-pituitary adrenal axis (HPA) plays an important role in the body’s response to stress; as shown in the above diagram, the HPA has a hierarchical structure with negative feedback signals as part of the control system. The authors report 6 variations of FKPB5 carry an increased risk of chronic pain following trauma. The findings suggest a neurological mechanism behind persistent pain following trauma, possibly related to a breakdown in the body’s stress response system. The research also lends support to chronic pain sufferers whose symptoms are often dismissed as “psychological” when doctors find no apparent cause.

The symptoms of PTSD can include aggression, hyper-vigilance, anxiety, chronic pain, depression, low serotonin and difficulty focusing. Stressed dogs show many of the same disturbances identified in humans including depressed levels of serotonin (León 2012).

There is nothing special or unique about the human stress response. The HPA is an old, well-conserved system that has been found in all studied vertebrates; some of the molecules involved in the signalling pathway are even older (Dores 2005).

For this reason there is no reason to think that a skewed HPA response and its association with chronic pain is unique to humans. There is plenty of evidence suggesting FKBP5 polymorphism similarly affects human and non-human animals; everything from impulsivity to stress response (Szklarczyk 2012, Klengel 2012).

Comparison of human and dog FKPB5. The BLACK bars shows where they are the same.

Comparison of human and dog FKPB5. The BLACK bars shows where they are the same.

So, is it possible that dogs experience chronic pain as a result of stress? Could some behavior problems seen in dogs be traced to a similar HPA dysregulation? Could certain breeds or lines be more susceptible to HPA disturbances?

While I’m not going to suggest some dogs who’ve had traumatic experiences will experience chronic pain (and possibly related aggression); I will put it forth as a possibility.

At the very least, it bears investigation.

REFERENCES

Bortsov AV, Smith JE, Diatchenko L, Soward AC, Ulirsch JC, Rossi C, Swor RA, Hauda WE, Peak DA, Jones JS, Holbrook D, Rathlev NK, Foley KA, Lee DC, Collette R, Domeier RM, Hendry PL, & McLean SA (2013). Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure. Pain PMID: 23707272

Dores R.M. & Lecaude S. Trends in the evolution of the proopiomelanocortin gene., General and comparative endocrinology, PMID: 

Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, Pace TW, Mercer KB, Mayberg HS, Bradley B, Nemeroff CB, Holsboer F, Heim CM, Ressler KJ, Rein T, & Binder EB (2013). Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature neuroscience, 16 (1), 33-41 PMID: 23201972

León M, García-Belenguer, Chacón G, Villegas A, Palacio J. (2012)Assessment of serotonin in serum, plasma, and platelets of aggressive dogs. Journal of Veterinary Behavior: Clinical Applications and Research. Volume 7, Issue 6 , Pages 348-352, November 2012

Szklarczyk K, Korostynski M, Golda S, Solecki W, & Przewlocki R (2012). Genotype-dependent consequences of traumatic stress in four inbred mouse strains. Genes, brain, and behavior PMID: 22974489  doi: 10.1111/j.1601-183X.2012.00850.x

Binder EB (2009). The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology, 34 Suppl 1 PMID: 19560279. doi: 10.1016/j.psyneuen.2009.05.021.

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