Induction of cervical disc degeneration and discogenic pain by low concentration Propionibacterium acnes infection: an in vivo animal study.

BACKGROUND: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. METHODS: Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. RESULTS: IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. CONCLUSION: P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.

Oxygen-Ozone Therapy in the Rehabilitation Field: State of the Art on Mechanisms of Action, Safety and Effectiveness in Patients with Musculoskeletal Disorders.

In recent years, the interest in oxygen-ozone (O2O3) therapy application has considerably increased in the field of rehabilitation. Despite its widespread use in common clinical practice, the biochemical effects of O2O3 are still far from being understood, although its chemical properties seem to play a pivotal role in exerting its positive effects on different pathological conditions. Indeed, the effectiveness of O2O3 therapy might be partly due to the moderate oxidative stress produced by O3 interactions with biological components. O2O3 therapy is widely used as an adjuvant therapeutic option in several pathological conditions characterized by chronic inflammatory processes and immune over-activation, and most musculoskeletal disorders share these pathophysiological processes. The present comprehensive review depicts the state-of-the-art on the mechanisms of action, safety and effectiveness of O2O3 therapy in the complex scenario of the management of musculoskeletal disorders. Taken together, our findings suggest that O2O3 therapy seems to reduce pain and improve functioning in patients affected by low back pain and knee osteoarthritis, as reported by several studies in the literature. However, to date, further studies are warranted to clearly investigate the therapeutic effects of this promising therapy on other musculoskeletal disorders in the field of rehabilitation.

Neuronal nitric oxide synthase is dislocated in type I fibers of myalgic muscle but can recover with physical exercise training.

Trapezius myalgia is the most common type of chronic neck pain. While physical exercise reduces pain and improves muscle function, the underlying mechanisms remain unclear. Nitric oxide (NO) signaling is important in modulating cellular function, and a dysfunctional neuronal NO synthase (nNOS) may contribute to an ineffective muscle function. This study investigated nNOS expression and localization in chronically painful muscle. Forty-one women clinically diagnosed with trapezius myalgia (MYA) and 18 healthy controls (CON) were included in the case-control study. Subsequently, MYA were randomly assigned to either 10 weeks of specific strength training (SST, n = 18), general fitness training (GFT, n = 15), or health information (REF, n = 8). Distribution of fiber type, cross-sectional area, and sarcolemmal nNOS expression did not differ between MYA and CON. However, MYA showed increased sarcoplasmic nNOS localization (18.8 ± 12 versus 12.8 ± 8%, P = 0.049) compared with CON. SST resulted in a decrease of sarcoplasm-localized nNOS following training (before 18.1 ± 12 versus after 12.0 ± 12%; P = 0,027). We demonstrate that myalgic muscle displays altered nNOS localization and that 10 weeks of strength training normalize these disruptions, which supports previous findings of impaired muscle oxygenation during work tasks and reduced pain following exercise.

Effects of two different specific neck exercise interventions on palmitoylethanolamide and stearoylethanolamide concentrations in the interstitium of the trapezius muscle in women with chronic neck shoulder pain.

PURPOSE: Chronic neck/shoulder pain (CNSP) is one of the most common pain conditions. The understanding of mechanisms, including the peripheral balance between nociceptive and antinociceptive processes, is incomplete. N-acylethanolamines (NAEs) are a class of endogenous compounds that regulate inflammation and pain. The aim of this study was to investigate the levels of two NAEs: the peroxisome proliferator-activated receptor type-α ligand palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) in the muscle interstitium of the trapezius muscle in women with CNSP randomized to two different neck specific training programs and in a healthy pain-free control group (CON). MATERIALS AND METHODS: Fifty-seven women with CNSP were randomized to strength + stretch or stretch alone exercise programs. Twenty-nine subjects underwent microdialysis procedure before and after 4-6 months of exercise. Twenty-four CON subjects underwent microdialysis procedure before and after 4-6 months without any intervention in between. Microdialysate samples were collected from the trapezius muscle and analyzed by mass spectrometry for PEA and SEA levels. RESULTS: PEA and SEA levels were significantly higher in CNSP patients compared with CON. PEA was significantly higher in CNSP than in CON after both training programs. SEA was significantly higher in CNSP than in CON after stretch alone but not after strength + stretch training. A significant positive correlation was found between changes in pain intensity and in SEA levels in the strength + stretch group, but not in the stretch alone group. CONCLUSION: Our results indicate that exercise interventions differentially affect the levels of the bioactive lipids PEA and SEA in the interstitium of the trapezius muscle in women with CNSP.

Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration.

STUDY DESIGN: In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs after painful whole-body vibration (WBV). OBJECTIVE: The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful WBV in a rat model. SUMMARY OF BACKGROUND DATA: WBV is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically, aneural regions of painful human lumbar discs exhibit hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc degeneration and pain. BDNF and NGF are upregulated in painfully degenerate lumbar discs and hypothesized to contribute to this pathology. METHODS: Male Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham exposures, followed by 7 days of rest. Cervical discs were collected for analysis of BDNF and NGF expression through RT-qPCR and Western blot analysis. Immunohistochemistry also evaluated their regional expression in the disc. RESULTS: Vibration significantly increases BDNF messenger ribonucleic acid (mRNA) levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold, respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035) levels are significantly correlated with the degree of behavioral sensitivity (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus. CONCLUSION: The increases in BDNF and NGF in the cervical discs after painful vibration are observed in typically aneural regions of the disc, consistent with reports of its hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not explicitly investigated. Neurotrophin expression also correlates with behavioral sensitivity, suggesting a role for both neurotrophins in the development of disc pain. LEVEL OF EVIDENCE: N/A.

Mode of action of cupping--local metabolism and pain thresholds in neck pain patients and healthy subjects.

OBJECTIVES: Cupping worldwide has been part of traditional medicine systems and is in the western world used as CAM therapy mainly for treating pain syndromes. The mode of action is up to now unclear. In order to investigate its mechanism we measured in parallel metabolic changes in the tissue under the cupping glass and pressure pain thresholds. DESIGN AND INTERVENTIONS: In 12 volunteers (6 healthy subjects and 6 patients with chronic neck pain) a microdialysis system was implanted subcutaneously on both sides (left and right) above the trapezius muscle. After baseline measures cupping was performed at one randomly selected side (left or right), the other side served as control. Every 20 min during baseline measures and for 280 min after cupping, microdialysis probes for detection of lactate, pyruvate, glucose and glycerin were taken. In addition, pain thresholds were measured before and after cupping with algometry. RESULTS: Cupping resulted in a strong increase of lactate (beginning 160 min after cupping until the end of the measurements) and the lactate/pyruvate ratio, indicating an anaerobe metabolism in the surrounding tissue. Baseline pain thresholds were non-significantly lower in neck pain patients compared to healthy controls and slightly increased immediately after cupping (p<0.05 compared to baseline close to the area of cupping in healthy subjects and on the foot in neck pain patients). After 280 min no more significant changes of pain thresholds were detected. CONCLUSIONS: Cupping induces >280 min lasting anaerobe metabolism in the subcutaneous tissue and increases immediate pressure pain thresholds in some areas.

[Effects of electroacupuncture at "Futu"(LI 18), etc. on pain threshold and cervico-spinal mGlu receptor 5/cAmp/CREB signaling in rats with neck incision pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Futu" (LI 18),etc. on the pain threshold and expression of metabotropic glutamate receptor subtype 5 (mGluR 5), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), cAMP responsive element binding protein (CREB) genes in the cervico-spinal dorsal region in rats with neck incision pain so as to analyze its underlying analgesic mechanism in performing thyroid surgery. METHODS: Forty male Wistar rats were randomly divided into control, model, Futu (LI 18), Hegu (LI 4)-Neiguan (PC 6), Zusanli (ST 36)-Yanglingquan (GB 34) groups, with 8 cases in each group. Neck-incision pain model was established by making a longitudinal incision along the midline of the neck under anesthesia (isoflurane) except rats in the control group. EA(2 Hz/15 Hz, 1-2 mA) was applied to bilateral LI 18, LI 4-PC 6 and ST 36-GB 34 for 30 min, 4 h, 24 h and 48 h after modeling, respectively. The thermal pain threshold was detected before modeling, and before and after each treatment. After removing the ventral part, the spinal tissue of the cervical 1 -4 segments was collected for detecting the expression of mGluR 5, cAMP, MAPK, CREB genes by using quantitative real-time-PCR technique. RESULTS: In comparison with the control group, the pain threshold of the model group was decreased obviously (P<0.05). Compared with the model group, the pain thresholds of the LI 18 and LI 4-PC 6 groups were upregulated markedly after treatment (P<0.05). No significant differences were found between the LI 18 and LI 4-PC 6 groups, and between the model and ST 36-GB 34 groups in pain thresholds (P>0.05). Compared with the control group, the expression le-vels of mGluR 5 mRNA, cAMP mRNA and CREB mRNA in the cervico-spinal cord were upregulated significantly in the model group (P<0.05). While in comparison with the model group, cervico-spinal cAMP mRNA, and CREB mRNA were down-regulated markedly (P<0.05) and mGluR 5 mRNA was down-regulated moderately (P>0.05) in the LI 18 group, rather than in the LI 4-PC 6 and ST 36-GB 34 groups (P>0.05). CONCLUSION: EA-LI 18 can significantly suppress neck incision pain induced pain reaction, which may be closely associated with its functions in down-regulating expression levels of intracellular cAMP mRNA and CREB mRNA in the cervico-spinal cord.

Effect of muscle load tasks with maximal isometric contractions on oxygenation of the trapezius muscle and sympathetic nervous activity in females with chronic neck and shoulder pain.

BACKGROUND: Sympathetic nervous activity contributes to the maintenance of muscle oxygenation. However, patients with chronic pain may suffer from autonomic dysfunction. Furthermore, insufficient muscle oxygenation is observed among workers with chronic neck and shoulder pain. The aim of our study was to investigate how muscle load tasks affect sympathetic nervous activity and changes in oxygenation of the trapezius muscles in subjects with chronic neck and shoulder pain. METHODS: Thirty females were assigned to two groups: a pain group consisting of subjects with chronic neck and shoulder pain and a control group consisting of asymptomatic subjects. The participants performed three sets of isometric exercise in an upright position; they contracted their trapezius muscles with maximum effort and let the muscles relax (Relax). Autonomic nervous activity and oxygenation of the trapezius muscles were measured by heart rate variability (HRV) and Near-Infrared Spectroscopy. RESULTS: Oxyhemoglobin and total hemoglobin of the trapezius muscles in the pain group were lower during the Relax period compared with the control group. In addition, the low frequency / high frequency (LF/HF) ratio of HRV significantly increased during isometric exercise in the control group, whereas there were no significant changes in the pain group. CONCLUSIONS: Subjects with neck and shoulder pain showed lower oxygenation and blood flow of the trapezius muscles responding to isometric exercise, compared with asymptomatic subjects. Subjects with neck and shoulder pain also showed no significant changes in the LF/HF ratio of HRV responding to isometric exercise, which would imply a reduction in sympathetic nervous activity.

Transient nerve root compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mGLuR5 expression.

Injury to the cervical nerve roots is a common source of neck pain. Animal models of nerve root compression have previously established the role of compression magnitude and duration in nerve root-mediated pain and spinal inflammation; yet, the response of the spinal glutamatergic system to transient nerve root compression and its relationship to compression mechanics have not been studied. The glutamate receptor, mGluR5, has a central role in pain, and its expression by neurons and astrocytes in the spinal cord may be pivotal for neuronal-glial signaling. This study quantified spinal GFAP and mGluR5 expression following nerve root compressions of different magnitudes and durations in the rat. Compression to the C7 nerve root was applied for a duration that was either above (10 min) or below (3 min) the critical duration for mediating afferent discharge rates during compression. To also test for the effect of the magnitude of the compression load, either a 10 gf or a 60 gf was applied to the nerve root for each duration. Mechanical allodynia was assessed, and the C7 spinal cord was harvested on day 7 for immunofluorescent analysis. Double labeling was used to localize the expression of mGluR5 on astrocytes (GFAP) and neurons (MAP2). Seven days after injury, 10 min of compression produced significantly greater behavioral sensitivity (P<0.001) and spinal GFAP expression (P=0.002) than 3 min of compression, regardless of the compression magnitude. Nerve root compression at 60 gf produced a significant increase (P<0.001) in spinal mGluR5 for both of the durations studied. There was no difference in the distribution of mGluR5 between astrocytes and neurons following nerve root compression of any type. The glutamatergic and glial systems are differentially modulated by the mechanics of nerve root compression despite the known contribution of glia to pain through glutamatergic signaling.

[Effect of electroacupuncture at different acupoints on expression of cervico-spinal GDNF and BDNF and their receptor genes in neck-incision pain rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Futu" (LI 18), etc. on the expression of genes of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and their receptors in the cervico-spinal cord in neck-incision pain rats, so as to study its mechanism underlying incision-pain relief. METHODS: A total of 50 Sprague Dawley male rats were randomly divided into normal, model (incision pain), EA-Futu (LI 18), EA- Hegu (LI 4) - Neiguan (PC 6, LI 4-PC 6) and EA-Zusanli (ST 36)-Yanglingquan (GB 34, ST 36-GB 34) groups (n = 10/group). A 1.5 cm long longitudinal incision was made along the midline of the neck under anesthesia to duplicate neck-incision pain model. Thermal pain threshold (PT) was measured before and after modeling and after the treatment, respectively. EA (1-2 mA, 2 Hz/100 Hz) was applied to bilateral LI 18, PC 6-LI 4 and ST 36-GB 34 for 30 min. The expression of genes of GDNF and its receptor GFRalpha-1, and BDNF and its receptors TrkA, TrkB in the spinal cord (C1 - C4) tissue was detected by quantitative real-time-PCR. RESULTS: In comparison with pre-modeling in the same one group, the thermal PT levels were decreased obviously in the model, LI 18, LI 4-PC 6 and ST 36-GB 34 groups after neck incision (P < 0.05). Compared with the model group, the PT levels were increased markedly in LI 18, LI 4-PC 6 and ST 36-GB 34 groups after the EA treatment (P < 0.05). Correspondingly, the expression levels of spinal GDNF mRNA and GFRalpha-1 mRNA were obviously lower, as well as BDNF mRNA was markedly higher in the model group than in the control group (P < 0.05), and those of TrkA mRNA and TrkB mRNA were increased slightly in the model group than in the control group (P > 0.05). In comparison with the model group, the expression levels of spinal GDNF mRNA and GFRalpha-1 mRNA were up-regulated considerably (P < 0.001), whereas those of BDNF mRNA, TrkA mRNA and TrkB mRNA were decreased slightly (P > 0.05) in the LI 18, LI 4-PC 6 and ST 36-GB 34 groups after EA treatment. CONCLUSION: EA stimulation can significantly suppress pain reaction of neck incision, which is closely associated with its effects in up-regulating the expression of GDNF and its receptor GFRalpha-1 genes in the cervical spinal cord (C1 - C4).

Comparison of the cortisol awakening response in women with shoulder and neck pain and women with fibromyalgia.

Shoulder and neck pain (SNP) and fibromyalgia syndrome (FMS), two musculoskeletal conditions of unknown pathogenesis, share some common features in terms of altered neuroendocrine responses, pain and stress perception. However, the pain distribution in SNP is localized, whereas in FMS is more widespread. Because regional musculoskeletal pain may represent an intermediate stage along a continuum towards widespread musculoskeletal pain we compared the cortisol awakening response (CAR) in women with SNP with the CAR in FMS patients and healthy controls (HC) in a controlled hospital-hotel setting. The aim of the study was to investigate whether SNP is related to a deviant regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Eighteen women with SNP, 29 female FMS patients, and 27 female HC participated in the study. Cortisol samples were collected upon awakening, 30 and 60 min later. Questionnaires measuring pain levels, sleeping problems, perceived stress, and psychological characteristics were administered to the participants. Compared with HC, women with SNP had a tendency towards higher cortisol levels, whereas FMS had lower cortisol levels. Adjustment for potential confounders did not influence the results. Women with SNP and FMS patients reported more health complaints, pain, and perceived stress than the HC, but women with SNP were less affected than the FMS patients. Women with SNP showed a tendency towards an elevated HPA axis activity compared with HC. The current findings may indicate that the hypercortisolism in regional musculoskeletal pain represent an intermediate stage towards the development of a hypocortisolism in widespread musculoskeletal pain.

High levels of N-palmitoylethanolamide and N-stearoylethanolamide in microdialysate samples from myalgic trapezius muscle in women.

BACKGROUND: N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-α ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls. METHODS: Eleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS). RESULTS: We were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls. CONCLUSION: This study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAE's in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.

Elevated production of inflammatory mediators including nociceptive chemokines in patients with neck pain: a cross-sectional evaluation.

OBJECTIVE: This study investigated whether the production of inflammatory mediators and chemotactic cytokines (chemokines) is altered in patients with chronic and recurrent neck pain (NP). METHODS: Cross-sectional data evaluating blood and serum samples were obtained from 27 NP patients and 13 asymptomatic (control) subjects recruited from a chiropractic outpatient clinic. Cell cultures were activated by lipopolysaccharide (LPS) and phytoheamagglutinin for 24 to 48 hours. The levels of tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1, also known as CCL2 (CCL2/MCP-1), and macrophage inflammatory protein 1α or CCL3 (CCL3/MIP-1α) were determined by specific immunoassays. Serum levels of nitric oxide metabolites were evaluated simultaneously, in vanadium III-reduced samples, by Griess reaction. RESULTS: Low levels of constitutive (spontaneous) TNF-α production were present in 7 of the 27 cultures from patients with NP. Both LPS-induced TNF-α production and inducer (LPS/phytoheamagglutin)-stimulated production of CCL2 were significantly elevated (P = .00) in patients compared with controls. In patients, the constitutive synthesis of CCL3 occurred significantly more frequently (P = .00) and ranged from 30 to more than 2000 pg/mL. Finally, serum levels of nitric oxide were significantly elevated (P = .00) in NP patients. CONCLUSIONS: Production of inflammatory mediators was consistently elevated in NP patients in this study, both in vitro and in vivo, and activation of inflammatory pathways was accompanied by up-regulation of CC chemokine synthesis. This suggests that, in NP patients, CC chemokines may be involved in regulation of local inflammatory response through recruitment of immune cells to the inflamed tissue and exert pronociceptive effects.

Are abnormalities in sarcoplasmic reticulum calcium cycling properties involved in trapezius myalgia?: case studies on three females.

OBJECTIVE: The aim of this study was to demonstrate the feasibility of using samples obtained through muscle biopsy to assess a wide range of cellular properties, some of which may be abnormal in myalgia. Given the recent emphasis on the role of excitation-contraction coupling in health and disease, special emphasis is given to the characterization of the properties involved in this process. DESIGN: Tissue samples were obtained from the upper portion of the descending trapezius muscle in three female patients (PAT) with clinically diagnosed myalgia and assessed for a spectrum of properties related to substrate use, energy production, and excitation-contraction coupling and were compared with samples from three healthy controls. RESULTS: At the level of organization of the metabolic pathways, all PAT generally displayed normal activities of enzymes representing the potential for oxidative phosphorylation, glucose phosphorylation, glycolysis, and lactate oxidation. In contrast, a reduced potential was observed in PAT for both fat oxidation (-20%) and high-energy phosphate transfer (-38%). For excitation-contraction coupling, PAT had a compromised sarcoplasmic reticulum maximal Ca-ATPase activity (-21%), Ca uptake (-44%), and sarcoplasmic endopleasmic reticulum (SERCA) expression for both SERCA1a (-16%) and SERCA2a (-17%), which were accompanied by a lower phase 2 Ca release (-45%). The Na-K-ATPase concentration, the enzyme-regulating membrane excitability via active Na and K seemed elevated (+25%) in PAT. CONCLUSIONS: These results demonstrate the feasibility of analyzing tissue samples for a wide range of properties and provide a rationale for studies examining the cellular basis of myalgia with particular emphasis on sarcoplasmic reticulum Ca cycling, given the latter's role in regulating a wide range of cellular functions.

Cerebral metabolic changes in men after chiropractic spinal manipulation for neck pain.

BACKGROUND: Chiropractic spinal manipulation (CSM) is an alternative treatment for back pain. The autonomic nervous system is often involved in spinal dysfunction. Although studies on the effects of CSM have been performed, no chiropractic study has examined regional cerebral metabolism using positron emission tomography (PET). OBJECTIVE: The aim of the present study was to investigate the effects of CSM on brain responses in terms of cerebral glucose metabolic changes measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twelve male volunteers were recruited. Brain PET scanning was performed twice on each participant, at resting and after CSM. Questionnaires were used for subjective evaluations. A visual analogue scale (VAS) was rated by participants before and after chiropractic treatment, and muscle tone and salivary amylase were measured. RESULTS: Increased glucose metabolism was observed in the inferior prefrontal cortex, anterior cingulated cortex, and middle temporal gyrus, and decreased glucose metabolism was found in the cerebellar vermis and visual association cortex, in the treatment condition (P < .001). Comparisons of questionnaires indicated a lower stress level and better quality of life in the treatment condition. A significantly lower VAS was noted after CSM. Cervical muscle tone and salivary amylase were decreased after CSM. Conclusion The results of this study suggest that CSM affects regional cerebral glucose metabolism related to sympathetic relaxation and pain reduction.

Metabotropic glutamate receptor-5 and protein kinase C-epsilon increase in dorsal root ganglion neurons and spinal glial activation in an adolescent rat model of painful neck injury.

There is growing evidence that neck pain is common in adolescence and is a risk factor for the development of chronic neck pain in adulthood. The cervical facet joint and its capsular ligament is a common source of pain in the neck in adults, but its role in adolescent pain remains unknown. The aim of this study was to define the biomechanics, behavioral sensitivity, and indicators of neuronal and glial activation in an adolescent model of mechanical facet joint injury. A bilateral C6-C7 facet joint distraction was imposed in an adolescent rat and biomechanical metrics were measured during injury. Following injury, forepaw mechanical hyperalgesia was measured, and protein kinase C-epsilon (PKCɛ) and metabotropic glutamate receptor-5 (mGluR5) expression in the dorsal root ganglion and markers of spinal glial activation were assessed. Joint distraction induced significant mechanical hyperalgesia during the 7 days post-injury (p < 0.001). Painful injury significantly increased PKCɛ expression in small- and medium-diameter neurons compared to sham (p < 0.05) and naïve tissue (p < 0.001). Similarly, mGluR5 expression was significantly elevated in small-diameter neurons after injury (p < 0.05). Spinal astrocytic activation after injury was also elevated over sham (p < 0.035) and naïve (p < 0.0001) levels; microglial activation was only greater than naïve levels (p < 0.006). Mean strains in the facet capsule during injury were 32.8 ± 12.9%, which were consistent with the strains associated with comparable degrees of hypersensitivity in the adult rat. These results suggest that adolescents may have a lower tissue tolerance to induce pain and associated nociceptive response than do adults.

Spinal pain and nutrition in adolescents--an exploratory cross-sectional study.

BACKGROUND: Spinal pain is an important health issue for adolescents resulting in functional limitations for many and increasing the risk of spinal pain in adulthood. Whilst human and animal studies suggest nutrition could influence spinal pain, this has not been investigated in adolescents. The objective of this exploratory cross sectional study was to evaluate associations between diet and adolescent spinal pain. METHODS: This study surveyed the spinal pain (neck and back) and nutrition (specific nutrients, broad food groups, diet quality and dietary pattern) of 1424 male and female adolescents at 14 years of age, in Western Australia. RESULTS: Back or neck pain were experienced by around half of the adolescents, with females more likely to experience spinal pain. Nutrition differed between sexes and deviated from optimal intakes. Vitamin B12, eggs, cereals and meat consumption were related to spinal pain in sex specific multivariate analyses including primary carer education level and adolescent waist girth and smoking. CONCLUSIONS: The findings of this study suggest that certain aspects of diet may have an association with spinal pain in adolescence.

Relationship between a chronically painful trapezius muscle and its metabolic state analyzed with PET/CT.

OBJECTIVES: The aim of this study was to investigate the intramuscular metabolic state in chronically painful muscles using positron-emission tomography/computerized tomography (PET/CT). STUDY DESIGN: The study included 140 consecutive noncancer subjects who underwent PET/CT screening for a physical checkup (mean age 56.0 +/- 10.22 y). The demographic data and information on pain in the neck/shoulder region were obtained using a questionnaire. The subjects who had an awareness of pain in the neck/shoulder region for >6 months were regarded to be pain subjects (n = 39). The minimal and maximal standardized uptake values (SUV) of [(18)F]fluorodeoxyglucose ((18)F-FDG) of the trapezius muscle in each subject were automatically calculated. RESULTS: The unpaired t test revealed that both the minimal and the maximal SUVs were significantly lower in the pain subjects than in the asymptomatic subjects. A multiple linear regression analysis also demonstrated a significant association between pain in the neck/shoulder region and the SUVs in the trapezius muscle. CONCLUSIONS: Uptake of (18)F-FDG was lower in the chronically painful trapezius muscle.