Spine-Adjusting Instrument (Impulse®) Attenuates Nociception and Modulates Oxidative Stress Markers in the Spinal Cord and Sciatic Nerve of a Rat Model of Neuropathic Pain.

OBJECTIVE: Oxidative stress plays an important role in neuropathic pain (NP). Spinal manipulative therapy (SMT) can exert beneficial effects on pain outcomes in humans and in animal models. SMT can also modulate oxidative stress markers in both humans and animals. We aimed to determine the effect of Impulse®-assisted SMT (ISMT) on nociception and oxidative stress biomarkers in the spinal cords and sciatic nerves of rats with NP. METHODS: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Animals were randomly assigned to naive, sham (rats with sciatic nerve exposure but without ligatures), or CCI, with and without ISMT. ISMT was applied onto the skin area corresponding to the spinous process of L4-L5, three times per week for 2 weeks. Mechanical threshold, latency to paw withdrawal in response to thermal stimulus, and oxidative stress biomarkers in the spinal cord and sciatic nerve were the main outcomes evaluated. RESULTS: ISMT significantly increased mechanical threshold and withdrawal latency after CCI. In the spinal cord, ISMT prevented the increase of pro-oxidative superoxide anion generation and hydrogen peroxide levels. Lipid hydroperoxide levels both in the spinal cord and in the sciatic nerve were attenuated by ISMT. Total antioxidant capacity increased in the spinal cords and sciatic nerves of CCI rats with and without ISMT. CCI and ISMT did not significantly change the total thiol content of the spinal cord. CONCLUSIONS: Our findings suggest that reduced oxidative stress in the spinal cord and/or nerve may be an important mechanism underlying a therapeutic effect of SMT to manage NP nonpharmacologically.

Peripheral oxidative stress blood markers in patients with chronic back or neck pain treated with high-velocity, low-amplitude manipulation.

OBJECTIVE: The purpose of this study was to investigate oxidative-stress parameters in individuals with chronic neck or back pain after 5 weeks of treatment with high-velocity, low-amplitude (HVLA) spinal manipulation. METHODS: Twenty-three individuals aged 38.2 ± 11.7 years with nonspecific chronic neck or back pain verified by the Brazilian Portuguese version of the Chronic Pain Grade, with a sedentary lifestyle, no comorbidities, and not in adjuvant therapy, underwent treatment with HVLA chiropractic manipulation twice weekly for 5 weeks. Therapeutic procedures were carried out by an experienced chiropractor. Blood samples were assessed before and after treatment to determine the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), and the levels of nitric oxide metabolites and lipid hydroperoxides. These blood markers were analyzed by paired Student t test. Differences were considered statistically significant, when P was <.05. RESULTS: There was no change in catalase but an increase in SOD (0.35 ± 0.03 U SOD per milligram of protein vs 0.44 ± 0.04 U SOD per milligram of protein; P < .05) and GPx (7.91 ± 0.61 nmol/min per milligram of protein vs 14.07 ± 1.07 nmol/min per milligram of protein; P < .001) activities after the treatment. The nitric oxide metabolites and the lipid hydroperoxides did not change after treatment. CONCLUSION: High-velocity, low-amplitude spinal manipulation twice weekly for 5 weeks increases the SOD and GPx activities. Previous studies have shown a relationship between pain and oxidative and nitrosative parameters; thus, it is possible that changes in these enzymes might be related to the analgesic effect of HVLA spinal manipulation.

Effect of high-velocity, low-amplitude treatment on superoxide dismutase and glutathione peroxidase activities in erythrocytes from men with neck pain.

OBJECTIVE: This study investigates the analgesic effect of high-velocity, low-amplitude (HVLA) manipulation and antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes of men with neck pain. METHODS: Twenty-two men with neck pain of mechanical origin who were aged 20 to 50 years, were nonsmokers, had a sedentary lifestyle, had no comorbidities, and were not in adjuvant therapy underwent 6 sessions of HVLA chiropractic manipulation 3 times a week for 2 weeks. Patients were treated by the same chiropractor and under the same conditions. Blood samples were collected before the beginning of the treatment and at the end of the third and last session. Erythrocytes were separated from blood and then processed to determine SOD and GPx activities. The quadruple visual scale and the Neck Disability Index were used to demonstrate the analgesic effect of treatment. The results were analyzed by repeated-measures analysis of variance followed by Bonferroni posttest. Differences were considered significant when P was less than .05. RESULTS: Despite the tendency to reduction in SOD and increase in GPx activities, there was no significant change after the treatment. CONCLUSION: High-velocity, low-amplitude treatment for 6 sessions in men with neck pain did not affect systemic SOD and GPx activities. Despite the absence of significant changes, this study is important because it is the first to investigate the activities of SOD and GPx in patients with neck pain treated with HVLA spinal manipulation.

Effects of high-velocity, low-amplitude manipulation on catalase activity in men with neck pain.

OBJECTIVE: The aim of this study was to identify the influence of high-velocity, low-amplitude (HVLA) manipulation on lipid peroxidation and catalase activity in subjects with neck pain who answered the Neck Disability Index and quadruple visual scale questionnaires. METHODS: Twenty-two men (mean age, 38 years) with neck pain were recruited through radio and newspaper advertisements in the local media. Every patient received 6 sessions of HVLA manipulation, 3 times a week for 2 weeks. Blood samples were drawn from the cubital vein before treatment in the first session and after the third and sixth sessions. The quadruple visual scale was used with the same scheme. The Neck Disability Index questionnaire was applied before the beginning of treatment and after the last session. Catalase activity and lipoperoxidation were measured in erythrocyte samples. RESULTS: Results showed no change in lipid peroxidation. Nevertheless, the catalase activity was increased by HVLA manipulation. The same treatment reduced pain perception and disability in these subjects. CONCLUSION: The present study has shown that catalase activity of the erythrocytes, but not lipoperoxidation, increased after 6 sessions of HVLA manipulation treatment in men with neck pain. The results support the beneficial role of HVLA in the treatment of patients with neck pain.

Low expression of MRP1/GS-X pump ATPase in lymphocytes of Walker 256 tumour-bearing rats is associated with cyclopentenone prostaglandin accumulation and cancer immunodeficiency.

Immunosuppression is a life-threatening complication of late cancer stages. In this regard, overproduction in the host plasma of the anti-inflammatory cyclopentenone prostaglandins (CP-PGs), which are strongly antiproliferative at high concentrations, may impair immune function. In fact, lymphoid tissues of tumour-bearing rats accumulated large amounts of CP-PGs while the tumour tissue itself did not. Expression of the CP-PG-induced 72-kDa heat shock protein (hsp70) was elevated in lymphocytes from tumour-bearing animals related to controls. As the capacity for CP-PG uptake by lymphocytes is the same as tumour cells, we investigated whether the latter could overexpress the multidrug resistance-associated protein (MRP1/GS-X pump) which extrudes CP-PGs towards the extracellular space as glutathione S-conjugates. Walker 256 tumour cells extruded 15-fold more S-conjugates than lymphocytes from the same rats (p < 0.001). This did not appear to be related to deficiency in lymphocyte glutathione (GSH) metabolism, since the major GSH metabolic routes are consistent with CP-PG conjugation in lymphocytes. This was not the case, however, for the MRP1/GS-X pump activity in lymphocyte membranes (in pmol/min/mg protein: 3.1 +/- 1.7 from normal rats, 0.2 +/- 0.2 from tumour-bearing animals vs 64.3 +/- 7.0 in tumour cells) which was confirmed by Western blot analysis for MRP1 protein. Transfection of lymphocytes with MRP1 gene completely abolished CP-PG (0-40 microM) toxicity. Taken together, these findings suggest that CP-PG accumulation in lymphocytes may be, at least partially, responsible for cancer immunodeficiency. Clinical approaches for overexpressing MRP1/GS-X pump in lymphocytes could then play a role as a tool for the management of cancer therapeutics.