For chronic neck pain, the use of strengthening exercise, whether in combination with spinal manipulation or in the form of a high-technology MedX program, appears to be more beneficial to patients with chronic neck pain than the use of spinal manipulation alone. The effect of low-technology exercise or spinal manipulative therapy alone, as compared with no treatment or placebo, and the optimal dose and relative cost effectiveness of these therapies, need to be evaluated in future studies.

The results of this study demonstrate an advantage of spinal manipulation combined with low-tech rehabilitative exercise and MedX rehabilitative exercise versus spinal manipulation alone over two years and are similar in magnitude to those observed after one-year follow-up. These results suggest that treatments including supervised rehabilitative exercise should be considered for chronic neck pain sufferers. Further studies are needed to examine the cost effectiveness of these therapies and how spinal manipulation compares to no treatment or minimal intervention.

Chronic low back pain (CLBP) remains one of the most difficult and costly medical problems in the industrialized world. A review of nineteenth and early twentieth century spine rehabilitation shows that back disorders were commonly treated with aggressive and specific progressive resistance exercise (PRE). Despite a lack of scientific evidence to support their efficacy, therapeutic approaches to back rehabilitation over the past 30 yr have focused primarily upon passive care for symptom relief. Recent spine rehabilitation programs have returned to active reconditioning PRE centered around low back strengthening to restore normal musculoskeletal function. Research has shown that lumbar extension exercise using PRE significantly increases strength and decreases pain in CLBP patients. It appears that isolated lumbar extension exercise with the pelvis stabilized using specialized equipment elicits the most favorable improvements in low back strength, muscle cross-sectional area, and vertebral bone mineral density (BMD). These improvements occur with a low training volume of 1 set of 8 to 15 repetitions performed to volitional fatigue one time per week. CLBP patients participating in isolated lumbar extension PRE programs demonstrate significant reductions in pain and symptoms associated with improved muscle strength, endurance, and joint mobility. Improvements occur independent of diagnosis, are long-lasting, and appear to result in less re-utilization of the health care system than other more passive treatments. Low back strengthening shows promise for the reduction of industrial back injuries and associated costs.

The role of ␣ 1 -adrenergic receptors (␣ 1 ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. ␣ 1A AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term ␣ 1A AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the ␣ 1A AR. CAM-␣ 1A AR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the ␣ 1A AR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-␣ 1A AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the ␣ 1A AR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-␣ 1A AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-␣ 1A AR mice was 10% longer than that of WT mice. Our results suggest that long-term ␣ 1A AR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.

Activation of G protein-coupled ␣ 2 adrenergic receptors (ARs) inhibits epileptiform activity in the hippocampal CA3 region. The specific mechanism underlying this action is unclear. This study investigated which subtype(s) of ␣ 2 ARs and G proteins (G␣ o or G␣ i ) are involved in this response using recordings of mouse hippocampal CA3 epileptiform bursts. Application of epinephrine (EPI) or norepinephrine (NE) reduced the frequency of bursts in a concentration-dependent manner: (Ϫ)EPI Ͼ (Ϫ)NE ϾϾϾ (ϩ)NE. To identify the ␣ 2 AR subtype involved, equilibrium dissociation constants (pK b ) were determined for the selective ␣AR antagonists atipamezole (8.79), rauwolscine (7.75), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride (WB-4101; 6.87), and prazosin (5.71). Calculated pK b values correlated best with affinities determined previously for the mouse ␣ 2A AR subtype (r ϭ 0.98, slope ϭ 1.07). Furthermore, the inhibitory effects of EPI were lost in hippocampal slices from ␣ 2A AR-but not ␣ 2C AR-knockout mice. Pretreatment with pertussis toxin also reduced the EPImediated inhibition of epileptiform bursts. Finally, using knock-in mice with point mutations that disrupt regulator of G protein signaling (RGS) binding to G␣ subunits to enhance signaling by that G protein, the EPI-mediated inhibition of bursts was significantly more potent in slices from RGS-insensitive G␣ o G184S heterozygous (G␣ o ϩ/GS) mice compared with either G␣ i2 G184S heterozygous (G␣ i2 ϩ/GS) or control mice (EC 50 ϭ 2.5 versus 19 and 23 nM, respectively). Together, these findings indicate that the inhibitory effect of EPI on hippocampal CA3 epileptiform activity uses an ␣ 2A AR/G␣ o protein-mediated pathway under strong inhibitory control by RGS proteins. This suggests a possible role for RGS inhibitors or selective ␣ 2A AR agonists as a novel antiepileptic drug therapy.