Genetic Variants Associated With the Occurrence of Localized Low Back Pain or Low Back Pain With Widespread Pain Symptoms, and Their Response to Treatment With Duloxetine or Propranolol

Low back pain disorders are reported in 19-21% of the North American population, with the majority of them associating pain and physical impairment. Patients with this illness have an increased utilization of medical services, higher incidence of lost work days and long-term disability, representing a significant burden to the healthcare system and the economy.

Within the population of CLBP patients, two broad subgroups can easily be identified in the clinical setting: the patients who present with CLBP as their only pain symptom, and patients that present with CLBP and also associate widespread painful symptoms. The presence of widespread painful symptoms in the setting of low back pain has been recognized as a strong predictor of chronicity, apart from this, patients in this subgroup are more commonly middle aged females, report higher intensity of pain, more emotional problems and sleep disorders amongst others.

A recent publication by Slate et al has described genetic differences in patients with Temporal Mandibular Disorder (TMD) that present with either localized or widespread painful symptoms. This study established a link between Single Nucleotide Polymorphisms (SNPs) associated to the Serotonin Receptor and patients with localized TDM, and the presence of SNPs associated to the T cell receptor with patients with TMD and widespread symptoms. CLBP and TMD are two chronic pain conditions that are commonly present together. Given the connection between these two chronic pain disorders, it is highly likely that the genetic association findings from Slate et al could also be present in the CLPB population.

The main purpose of this study is to determine if CLBP patients presenting with either localized or widespread painful symptoms respond differently to treatment with Duloxetine, a Serotonin and Norepinephrine Reuptake Inhibitor (SNRI), and if the effectiveness of treatment with this drug can determined by the presence or absence of SNPs associated with the Serotonin receptor.

Another novel treatment alternative for patients with CLBP is Propranolol. This drug is a non-selective beta blocker that has also been shown to have analgesic effects on TMD. These effects though, are only present in patients carrying haplotypes associated with low activity of catechol-O-methyltransferase (COMT). The effect of beta blockers as analgesics has not yet been fully characterized, in animal models, catecholamine stimulation of beta 2 and beta 3 adrenoreceptors has shown to produce hyperalgesia and allodynia, on the other hand, in the clinical setting, the beta 1 selective blocker Esmolol has also been shown to have an analgesic effect in postoperative acute pain management. The inclusion of Propranolol as one of the treatment arms of this study will help elucidate Propranolol's possible role in chronic pain management; the expectation being that a more prominent analgesic effect will be found in patients displaying low activity COMT haplotypes.