Chronic back pain: searching for causes and cures.

Back pain is one of the 3 most common reasons for healthcare visits, with an episode in perhaps up to 75% of the population at some point1. Most acute back pain resolves within one to 3 months, but up to 15% of patients have persisting pain one year after an initial episode, while communitybased surveys repeatedly report that at least 5% of the population complains of daily or almost daily back pain for 6 months or more (i.e., chronic back pain)1. For most patients there are few treatment alternatives; worse yet, complete relief is rare. Several factors help explain this state of affairs. One is that the etiopathogenesis and mechanisms leading to the majority of chronic back pain syndromes are unknown. The list of potential risk factors for back pain chronicity, encompassing a broad array of demographic, behavioral, and social risks, ranges from smoking and obesity, to occupations requiring manual labor or long-haul driving, to job dissatisfaction2,3. The medical differential diagnosis of persisting back pain is similarly lengthy, beginning with nonspinal pathology that may present with back pain, as well as a search for serious underlying spinal disorders (the socalled “red flags” of vertebral fracture, spinal tumor or infection, or cauda equina syndrome)1. For most chronic back pain patients, however, a definitive pathoanatomic diagnosis cannot be made1, so one is left with collective diagnosis such as “nonspecific” back pain, musculoskeletal “strain,” or “degenerative disk disease. ” Degenerative change of intervertebral disks begins early in life (mid-twenties), is nearly universal by age 50, yet is asymptomatic in the majority of individuals, or only weakly correlated with symptoms. It is noted that degeneration covers so many clinical, radiologic, and pathologic processes that the term is simply a symbol of ignorance4. Many chronic back cases commence with what appears to be trivial soft tissue or neural injury. The persistence of pain beyond the period of expected healing is hypothesized to result from neuronal hyperactivity, changes in membrane excitability, dysfunction of modulatory or inhibitory systems, central sensitization, or expression of new genes resulting in abnormal processing of normal afferent traffic1, which possibly involve inflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α), interleukins], mitogen-activated protein kinases (MAPK), and prostaglandins (PG). Unfortunately there is not yet a widely accepted animal model of chronic back pain to help guide research. Given this atmosphere of uncertainty over etiopathogenesis and diagnosis, treatments proliferated and therapy became empiric. Over 20 years ago a seminal article proposed guidelines for distinguishing “useful from useless” therapy for low back pain5. Methodological criteria thought to be essential for establishing the validity and generalizability of outcome research for low back pain were: (1) a representative clinical sample described in demographic and clinical detail; (2) reporting of relevant outcomes, including physical symptoms, function, and psychological status; (3) random allocation; (4) blind outcome assessment; (5) documentation and assurance of equality of cointerventions; (6) measurement of compliance; (7) efforts to eliminate or to identify and quantify contamination of study groups by patients obtaining study treatments elsewhere; and (8) rigorous consideration of statistical and clinical significance of outcome. Refinements were added subsequently. Because side effects were observed to be associated with placebo analgesia in chronic pain — and chronic back pain particularly was thought to be placebo-responsive — “active” placebos became the state of the art in back pain research to assure blinding6, especially if the study drug produced obvious side effects like dry mouth, sedation, or nausea. Finally, to evaluate the integrity of the blind it was noted that study subjects (and the blinded study physician) should be asked to guess the study assignment at exit7. Although the quality of clinical trials for chronic back pain has improved remarkably in recent years, the field remains underserved. The medical mainstays of treatment, in usual order of use, have been nonsteroidal antiinflamma-