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10 Articles in Volume 10, Issue #1
An Overview of CRPS
Balancing Evidence, Efficacy and Stakeholder Values in Practical Pain Care
Biopsychosocial Approach to Management of Total Joint Arthroplasty Patients
Dextrose Prolotherapy Injections for Chronic Ankle Pain
Genetic Influences on Pain Perception and Treatment
Headache in Children and Adolescents
Hormone Replacements and Treatments in Chronic Pain: Update 2010
Opioid Treatment 10-year Longevity Survey Final Report
Therapeutic Laser in the Treatment of Herpes Zoster
Use and Effectiveness of Spinal Cord Stimulation

Genetic Influences on Pain Perception and Treatment

Genomic variations influence basal pain sensitivity and the likelihood of developing chronic pain so it is logical that the future of medicine is to provide more focused treatment based on a person's genetic code.
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The 2003 Narita study8 found increased rates of mutation in the serotonin transporter gene that results in increased serotonin uptake. By reducing serotonin levels in the synapses of the nerves, this mutation could also lead to reduced serotonin activity in CFS. This reduction in serotonin receptor activity could cause disturbances in sleep, pain, motivation, anxiety, depression, and sexual activity. Low serotonin levels contribute to decreased gastric emptying in CFS. Serotonin also affects the distribution of body fat and is being investigated for its link to the increased waist/height ratio found in CFS. This further supports the hypothesis that there is a direct correlation between the number of adipocytes and the amount of perceived pain.

Low Back Pain

Low back pain (LBP) is second only to the common cold as a problem that brings a patient to their primary care provider. LBP is the number one cause of disability in the industrialized world.9 Back pain has a substantial impact on lifestyle and quality of life. A 2006 U.S. survey found that 72 percent of those who sought treatment for back pain gave up on exercising or sports-related activities. Sixty percent said they were unable to perform some daily activities, and 46 percent said they had given up sex because of their back condition.10 LBP is a complex entity of pathophysiological, mechanical, psychological, and social factors. Epidemiological evidence suggests the following risk factors for LBP: disc degeneration, physical and psycho-social stress, increased weight, and smoking. Several studies have demonstrated familial predisposition for LBP.9

Several recent findings suggest a possible contribution of the IL-1 gene polymorphisms to low back pain. In chronic back pain, a SNP of the endogenous IL-1 receptor antagonist (IL-1Ra) from G to A at nucleotide position 1812 is associated with the occurrence of pain, the number of days with pain, and the number of days with limitation of daily activities. A SNP of IL-1-beta (IL-1ß) at nucleotide 3954 from C to T is associated with the number of days with pain. Furthermore, a C to T substitution at nucleotide 889 has been linked to pain intensity.

IL-1ß has a number of pro-inflammatory properties relevant to the pathogenesis of LBP. IL-1ß causes pain directly or through increasing sensitivity to other pain producing substances, such as bradykinin-a neuropeptide linked to pain mechanisms. The study by Kang et al11 showed pro-inflammatory exaggerated release of nitric oxide, IL-6, and prostaglandin ß2, which promotes inflammation from herniated discs upon stimulation with IL-1ß.9 It has been recently shown that peripheral inflammation causes an induction of cyclooxygenase-2 (cox-2), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. IL-1ß is observed to be a major inducer of central cox-2 upregulation by neurons in the brain and spinal cord as well as synthesis of prostaglandin E2 within the brain.9 Thus, in addition to the local regulatory function in inflammatory processes, IL-1 may be involved in the regulation of the pain response.

IL-1 is produced in the degenerate invertebral disc (IVD). It is normally produced by the native chondrocyte-like cells but, in the non-degenerate IVD, there is a balance between IL-1 and inhibitor, IL-1Ra, ensuring that matrix homeostasis is maintained. In a study where IVD cells were given IL-1, the normal balance of catabolic and anabolic events are disturbed. The degrading enzymes were increased, and the gene expression for matrix proteins was decreased. In addition, this study demonstrated that although numbers of cells with immunopositivity for the IL-1 agonists increased with degeneration, no such increase was seen in the numbers of cells with immunopositivity for IL-1Ra.12 This finding suggests that the normal inhibitory mechanism fails in disc degeneration, with a loss in the balance of IL-1 agonists to antagonists, allowing IL-1 to elicit and perpetuate a response. IL-1 causes cells from degenerate IVD’s to synthesize more IL-1, with the potential to induce accelerating degeneration. IL-1, a naturally occurring cytokine within the IVD could, through an imbalance between it and its inhibitor, play a role in the pathogenesis of IVD degeneration and therefore be an important therapeutic target for preventing and reversing disc degeneration.


Pain has diverse etiologies, mechanisms, and characteristics, and causes variable responses that are interpreted differently among individuals. Genomic variations influencing basal pain sensitivity and the likelihood of developing chronic pain diseases have been noted and continue to be studied. When treating pain, there are several factors to address. Think of pain as a tower of cards. The bottom layer is environmental and psychosocial factors. The second layer are the variations in nociception. The third is variations in the transmission of these signals. The fourth is the response that the pain transmission produces. The fifth is the chain reaction of system that has gone awry and causes chronic pain. The sixth is the interpretation of an individual’s pain. The top is the clinicians’ treatment of pain and is contingent upon understanding the underlying structure since without it treatment of the patient’s pain will limited, at best.

Genomics is developing a more granular understanding at each level and will ultimately lead to individualized pain management therapies. Suppose two people walk into a clinician’s office, both complaining of non-radiating low back pain. A clinician is apt to treat them the same. What if the clinician knew that one patient lacked IL-1Ra or had faulty ß2 receptors and the other did not? In this situation, the patients would more likely be treated differently, as the therapeutic agent that provides the most relief would be different. The future of medicine is providing more focused treatment based on a person’s genetic code. This understanding will allow clinicians to hone in on optimal treatment earlier in the individual’s quest for pain relief.

Last updated on: February 25, 2011