Chronic pain is associated with reduced brain gray matter and impaired cognitive ability. In this longitudinal study, we assessed whether neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes. We acquired MRI scans from chronic low back pain (CLBP) patients before (n ϭ 18) and 6 months after (spine surgery or facet joint injections; n ϭ 14) treatment. In addition, we scanned 16 healthy controls, 10 of which returned 6 months after the first visit. We performed cortical thickness analysis on structural MRI scans, and subjects performed a cognitive task during the functional MRI. We compared patients and controls, as well as patients before versus after treatment. After treatment, patients had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls. Increased DLPFC thickness correlated with the reduction of both pain and physical disability. Additionally, increased thickness in primary motor cortex was associated specifically with reduced physical disability, and right anterior insula was associated specifically with reduced pain. Left DLPFC activity during an attention-demanding cognitive task was abnormal before treatment, but normalized following treatment. These data indicate that functional and structural brain abnormalities-specifically in the left DLPFC-are reversible, suggesting that treating chronic pain can restore normal brain function in humans.

Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear underlying mechanisms. In humans and rodents, decreased expression of secreted protein acidic rich in cysteine (SPARC) is associated with intervertebral disc (IVD) degeneration and signs of LBP. The current study investigates the hypothesis that IVD degeneration is a risk factor for chronic LBP. SPARC-null and age-matched control mice ranging from 6 to 78 weeks of age were evaluated in this study. X-ray and histologic analysis revealed reduced IVD height, increased wedging, and signs of degeneration (bulging and herniation). Cutaneous sensitivity to cold, heat, and mechanical stimuli were used as measures of referred (low back and tail) and radiating pain (hind paw). Region specificity was assessed by measuring icilin- and capsaicin-evoked behaviour after subcutaneous injection into the hind paw or upper lip. Axial discomfort was measured by the tail suspension and grip force assays. Motor impairment was determined by the accelerating rotarod. Physical function was evaluated by voluntary activity after axial strain or during ambulation with forced lateral flexion. SPARC-null mice developed (1) region-specific, age-dependent hypersensitivity to cold, icilin, and capsaicin (hind paw only), (2) axial discomfort, (3) motor impairment, and (4) reduced physical function. Morphine (6 mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and challenging nature of LBP in humans and incorporate both anatomic and functional components of the disease. The current study supports the hypothesis that IVD degeneration is a risk factor for chronic LBP.

No abstract

The present data and data from the literature review suggest that there are several potential treatments for chemotherapy-evoked neuropathic pain. Nonsteroidal anti-inflammatory drugs have little or no efficacy. Opioids have an effect, but probably only with high doses. At least some antidepressants are analgesic in these conditions. Some, but clearly not all, anticonvulsants and sodium channel blockers have efficacy. Tramadol is a particularly promising candidate. Topiramate, acetyl-L-carnitine, carbamazepine, and venlafaxine may have protective or restorative effects. Clinical trials of these candidates are needed to advance the treatment of chemotherapy-evoked pain.

Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains elusive. Comorbid conditions including anxiety, depression, and cognitive impairment further impact quality of life. Chronic pain is associated with reversible changes in brain anatomy and function and with long-term changes in gene expression. Epigenetic mechanisms, including DNA methylation, contribute to wide-spread and long-lasting reprogramming of gene expression. We previously reported decreases in global DNA methylation in the mouse frontal cortex 6 months after induction of neuropathic pain using the spared nerve injury (SNI) model. Here, we examined the therapeutic effect of increasing DNA methylation using the methyl donor S-adenosylmethionine (SAM). S-adenosylmethionine is marketed as a nutritional supplement for a range of conditions including liver disease, depression, osteoarthritis, fibromyalgia, and dementia. Three months after SNI or sham surgery, animals were treated with SAM (20 mg/kg, 3×/week) or saline orally for 4 months, and the impact on sensory, motor, motivational, and cognitive indices was measured. S-adenosylmethionine attenuated SNI-induced mechanical hypersensitivity and reduced active avoidance of mechanical stimuli but had no effect on cold sensitivity or motor capacity. S-adenosylmethionine completely blocked nerve injury-induced cognitive impairment and attenuated SNI-induced decreases in global DNA methylation in the frontal cortex. In summary, chronic oral administration of the methyl donor, SAM, attenuated sensory and cognitive symptoms associated with nerve injury in mice. These effects may be mediated, in part, through modulation of DNA methylation in the central nervous system by systemic administration of the methyl donor SAM.