The role of genetics in the causes and perception of back pain
In the first of a three-part review of the role of genetics in the causes and perception of back pain, Iona Collins, Suzanne Docherty, Ray Iles and Masood Shafafy look at how pain is perceived and the structural causes of back pain
PART I: PAIN PERCEPTION AND AN OVERVIEW OF STRUCTURAL CAUSES OF BACK PAIN
Most adults will experience some sort of backache during their lifetime. In most cases, the pain is a self-limiting episode, but a minority of people experience intrusive pain of a chronic or recurring nature, which conveys social and economic disadvantages. Most non-specific backache has a non-specific cause, therefore, management of this condition is difficult. With the advent of gene mapping and ease of obtaining genetic data from venous blood samples, many studies are being published which suggest that non-specific backache may have a genetic influence. Also, more research into genetic associations of pain behaviour indicates that genetic polymorphisms appear to influence both pain perception and postoperative outcome following surgery for backache. These observations may lead to future individualised gene therapy.
A genetic predisposition to backache is one of the strongest predictors of chronic disabling backache [1]. Other factors also contribute, including variations in pain perception – a phenomenon which also has a genetic influence [2]. Occasionally, the backache is specifically due to an identifiable structural cause, such as acute backache secondary to a lumbar vertebral fracture. A proportion of people with chronic backache also have a specific structural and identifiable cause – backache can be derived from any spinal structure, or referred pain from posterior mediastinal structures, such as a bleeding abdominal aortic aneurysm, or a manifestation of systemic disease, such as ankylosing spondylitis. The predisposition to have a dissecting aortic aneurysm [3] or developing ankylosing spondylitis [4] also has a genetic basis.
Epidemiologic studies have shown that the prevalence of back pain differs between rural and urban communities, as well as between developing versus developed countries [5,6]. Detailed reports of backache, however, have been hampered by the lack of a universally agreed definition for this symptom. As an example of how big the backache issue appears to be in the developed world, the point prevalence of self-reported non-specific backache in the USA is 30% [5]. From an economic viewpoint, backache is the underlying cause of an estimated 12.5 per cent of all absence from work due to sickness in the UK [7].
Pain behaviour from a genetic and anatomical viewpoint
The anatomy and function of chronic pain sufferers’ brains differ from the normal population [8]. These differences have been established in people diagnosed with chronic low back pain [9], fibromyalgia [10], regional pain disorders [11] and irritable bowel syndrome [12]. Apkarian and associates showed reduced volumes of grey matter in the pre-frontal cortices and thalami of patients suffering with chronic low back pain – the changes were more striking in those patients who suffered with neuropathic pain rather than non-neuropathic pain. Also, the grey matter differences appeared to correlate with duration of the reported chronic pain [9].
However, it appears that structural brain changes are a consequence rather than a cause of chronic pain. A study by Rodriguez-Raecke et al. [13] demonstrated reversal of brain changes in a person with chronic pain from an osteoarthritic hip, which was subsequently treated with joint replacement. Similarly, Gwilym et al. showed that 16 patients with hip osteoarthritis demonstrated thalamic atrophy; however, the thalamic volume was restored to normal values at nine months following removal of the pain source by means of a total hip arthroplasty [14]. In conclusion, it appears that structural brain changes associated with chronic pain are seen as a consequence of the pain stimulus.
Certain pain syndromes have proven causal genetic mutations. Extreme pain disorder and erythermalgia are caused by a mutation in the Nav 1.7 voltage-gated sodium channel causing a gain of function. Both disorders are peripherally mediated dysfunctional pain diseases, with a known genetic and molecular cause [15]. Family studies have revealed clusters of low back pain sufferers; however, twin studies have failed to demonstrate a genetic link [16]. This could be due to the very loose definition of low back pain, which does not distinguish between acute and chronic back pain.
A further factor for consideration is the pharmacological influence of chronic pain and its effect on the brain. A recent study demonstrated that when people with chronic back pain took 30mg of oral morphine daily for one month, the reward an