Ultra-Low Frequency Transcutaneous Electrical Nerve Stimulation on Pain Modulation in a Rat Model with Myogenous Temporomandibular Dysfunction.

Masticatory myofascial pain (MMP) is one of the most common causes of chronic orofacial pain in patients with temporomandibular disorders. To explore the antinociceptive effects of ultra-low frequency transcutaneous electrical nerve stimulation (ULF-TENS) on alterations of pain-related biochemicals, electrophysiology and jaw-opening movement in an animal model with MMP, a total of 40 rats were randomly and equally assigned to four groups; i.e., animals with MMP receiving either ULF-TENS or sham treatment, as well as those with sham-MMP receiving either ULF-TENS or sham treatment. MMP was induced by electrically stimulated repetitive tetanic contraction of masticatory muscle for 14 days. ULF-TENS was then performed at myofascial trigger points of masticatory muscles for seven days. Measurable outcomes included maximum jaw-opening distance, prevalence of endplate noise (EPN), and immunohistochemistry for substance P (SP) and µ-opiate receptors (MOR) in parabrachial nucleus and c-Fos in rostral ventromedial medulla. There were significant improvements in maximum jaw-opening distance and EPN prevalence after ULF-TENS in animals with MMP. ULF-TENS also significantly reduced SP overexpression, increased MOR expression in parabrachial nucleus, and increased c-Fos expression in rostral ventromedial medulla. ULF-TENS may represent a novel and applicable therapeutic approach for improvement of orofacial pain induced by MMP.

Ultrasound Acupuncture for Oxaliplatin-induced Peripheral Neuropathy in Patients With Colorectal Cancer: A Pilot Study.

BACKGROUND: Oxaliplatin is frequently used in the treatment of metastatic colorectal cancer. However, peripheral neuropathy is a severe adverse effect of oxaliplatin that may persist and impact quality of life. OBJECTIVE: To assess the potential effects of ultrasound acupuncture for the alleviation of symptoms related to oxaliplatin-induced peripheral neuropathy (OIPN) among patients with metastatic colorectal cancer. DESIGN: Prospective cohort pilot study. SETTING: Education and research hospital. PARTICIPANTS: Patients with a diagnosis of stage II-IV colorectal cancer undergoing oxaliplatin-based treatment regimens who experienced OIPN symptoms (n = 17). INTERVENTIONS: Pulsed therapeutic ultrasound (1 MHz) at bilateral acupuncture points of PC6, PC7, BL60, and KI1 was administered for 5 minutes per point daily for 12 days. MAIN OUTCOME MEASUREMENTS: Pain Quality Assessment Scale (PQAS), Chemotherapy-induced Neurotoxicity Questionnaire (CINQ), quantitative touch-detection threshold, cold-trigger pain withdrawal latency, and quality of life (EORTC QLQ-C30) were measured at baseline (day 0), pre-intervention (day 12, post wash-out period), post-intervention (day 24), and final follow-up (day 54). A P value of less than .05 was considered statistically significant. RESULTS: Scores of PQAS and CINQ significantly improved after ultrasound acupuncture at post-intervention and follow-up compared to both baseline and pre-intervention. Similar trends were also observed for the quantitative sensory testing, where touch-detection threshold significantly decreased and cold-trigger pain withdrawal latency significantly increased after ultrasound acupuncture. Patients also showed an improvement on quality of life outcomes as measured by QLQ-C30 post-intervention and at follow-up. CONCLUSIONS: Ultrasound acupuncture could be an effective intervention for OIPN symptoms for patients with colorectal cancer. However, larger and randomized clinical trials with placebo controls are needed to confirm such effects.

Effects of hippotherapy on body functions, activities and participation in children with cerebral palsy based on ICF-CY assessments.

PURPOSE: To evaluate the effects of hippotherapy on body functions, activities, and participation in children with CP of various functional levels by using the International Classification of Functioning, Disability and Health-Children and Youth (ICF-CY) checklist. METHODS: Fourteen children with cerebral palsy (CP) (3-8 years of age) were recruited for a 36-week study composed of baseline, intervention, and withdrawal phases (12 weeks for each phase, ABA design). Hippotherapy was implemented for 30 min once weekly for 12 consecutive weeks during the intervention phase. Body Functions (b) and Activities and Participation (d) components of the ICF-CY checklist were used as outcome measures at the initial interview and at the end of each phase. RESULTS: Over the 12 weeks of hippotherapy, significant improvements in ICF-CY qualifiers were found in neuromusculoskeletal and movement-related functions (b7), mobility (d4) and major life areas (d8) and, in particular, mobility of joint functions (b710), muscle tone functions (b735), involuntary movement reaction functions (b755), involuntary movement functions (b765), and play (d811) (all p < 0.05) when compared with baseline. CONCLUSION: This study demonstrated the beneficial effects of hippotherapy on body functions, activities, and participation in children with CP. Implications for Rehabilitation ICF-CY provides a comprehensive overview of functioning and disability and constitutes a universal language for identifying the benefits of hippotherapy in areas of functioning and disability in children with CP. In children with CP, hippotherapy encourages a more complementary approach that extends beyond their impairments and limitations in body functions, activities, and participation. The effect of hippotherapy was distinct from GMFCS levels and the majority of improvements were present in children with GMFCS levels I-III.

Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: a pilot prospective cohort study.

BACKGROUND: Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers. METHODS: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9, LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12 sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy-induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity scale (OSNS), quantitative touch-detection threshold (using von Frey filaments), and cold-triggered pain withdrawal latency (using the cold-water immersion test) were measured before and after completion of the 12 treatment sessions. RESULTS: PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold-trigger pain withdrawal latency all improved significantly after LA in the cancer patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced cold and mechanical allodynia and also decreased the incidence and severity of neurotoxicity symptoms in the patients' upper and lower extremities and impact on their daily activities (all p<0.05). CONCLUSIONS: Following treatment with LA, neurotoxicity symptoms were significantly improved in cancer patients with OIPN. Further randomised controlled trials are needed to evaluate the role of LA as a therapeutic option in the management of OIPN.

Acupuncture at distant myofascial trigger spots enhances endogenous opioids in rabbits: a possible mechanism for managing myofascial pain.

BACKGROUND AND AIM: Acupuncture applied at myofascial trigger points (MTrPs) of distant anatomical regions, to reduce pain in a patient's area of primary complaint, is one strategy that is available to manage myofascial pain. However, the endogenous opioid-mediated analgesic mechanism of distant acupuncture associated with pain control is still unclear. This aims of this study were to evaluate the changes in enkephalin and ß-endorphin in serum, spinal cord, dorsal root ganglion (DRG) and muscle induced by acupuncture at distant myofascial trigger spots (MTrSs, similar to human MTrPs) in rabbits, to explore its underlying remote analgesic mechanism. METHODS: Acupuncture at MTrSs of a distant muscle (gastrocnemius) was performed either for one session or five daily sessions in rabbits. The levels of enkephalin and ß-endorphin in proximal muscle (biceps femoris), serum, DRGs and spinal cords (L5-S2) were then determined by immunoassay immediately and 5 days after treatment. RESULTS: Immediately after treatment, acupuncture comprising both one dose and five doses significantly enhanced spinal enkephalin expression and serum ß-endorphin levels (p<0.05). However, only five-dose acupuncture significantly enhanced the ß-endorphin levels in the biceps femoris and DRGs (p<0.05), while 1-dose acupuncture did not (p>0.05). Furthermore, 5 days after treatment, significantly increased levels of spinal enkephalin and serum ß-endorphin persisted in animals that received 5-dose acupuncture (p<0.05). CONCLUSIONS: This study demonstrates that interactions within the endogenous opioid system may be involved in the remote effects of acupuncture treatment and could be a potential analgesic mechanism underlying MTrP pain management.

Synergistic effects of low-level laser and mesenchymal stem cells on functional recovery in rats with crushed sciatic nerves.

Transplantation of mesenchymal stem cells (MSCs) has been proposed to exert beneficial effects on peripheral nerve regeneration after a peripheral nerve injury, but the functional recovery in the denervated limb is still limited. In this study, we used low-level laser therapy (LLLT) as an adjunct therapy for MSC transplantation on the functional recovery of crushed sciatic nerve in rats. Peripheral nerve injury was induced in 48 Sprague-Dawley rats by crushing the unilateral sciatic nerve, using a vessel clamp. The animals with crushed injury were randomly divided into four groups: control group, with no treatment; MSC group, treated with MSC alone; LLLT group, treated with LLLT alone; and MSCLLLT group, treated with a combination of MSC and LLLT. The sciatic function index (SFI), vertical activity of locomotion (VA) and ankle angle (AA) of rats were examined for functional assessments after treatment. Electrophysiological, morphological and S100 immunohistochemical studies were also conducted. The MSCLLLT group showed a greater recovery in SFI, VA and AA, with significant difference from MSC, LLLT and control groups (p < 0.05). Moreover, markedly enhanced electrophysiological function and expression of S100 immunoreactivity, as well as fewer inflammatory cells and less vacuole formation were also demonstrated after nerve crush injury in the MSCLLLT group when compared with the groups receiving a single treatment (p < 0.05). MSC transplantation combined with LLLT could achieve better results in functional recovery than a conventional treatment of MSC or LLLT alone. LLLT has a synergistic effect in providing greater functional recovery with MSC transplantation after nerve crush injury.

Fluence-dependent effects of low-level laser therapy in myofascial trigger spots on modulation of biochemicals associated with pain in a rabbit model.

Evidence strongly supports that low-level laser therapy (LLLT) is an effective physical modality for the treatment of pain associated with myofascial trigger points (MTrP). However, the effect of laser fluence (energy intensity in J/cm(2)) on biochemical regulation related to pain is unclear. To better understand the biochemical mechanisms modulated by high- and low-fluence LLLT at myofascial trigger spots (MTrSs; similar to human MTrPs) in skeletal muscles of rabbits, the levels of ß-endorphin (ß-ep), substance P (SP), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) were investigated in this study. New Zealand rabbits (2.5-3.0 kg in weight) were used in this study. High-fluence LLLT (27 J/cm(2)), low-fluence LLLT (4.5 J/cm(2)), or sham operations were applied on MTrSs of biceps femoris of rabbits for five sessions (one session per day). Effects of LLLT at two different fluences on biceps femoris, dorsal root ganglion (DRG), and serum were determined by ß-ep, SP, TNF-α, and COX-2 immunoassays. LLLT irradiation with fluences of 4.5 and 27 J/cm(2) at MTrSs can significantly reduce SP level in DRG. LLLT with lower fluence of 4.5 J/cm(2) exerted lower levels of TNF-α and COX-2 expression in laser-treated muscle, but LLLT with higher fluence of 27 J/cm(2) elevated the levels of ß-ep in serum, DRG, and muscle. This study demonstrated fluence-dependent biochemical effects of LLLT in an animal model on management of myofascial pain. The findings can contribute to the development of dosage guideline for LLLT for treating MTrP-induced pain.

The fluence effects of low-level laser therapy on inflammation, fibroblast-like synoviocytes, and synovial apoptosis in rats with adjuvant-induced arthritis.

OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. BACKGROUND DATA: Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence effects of LLLT on synovium are unclear. METHODS: Monoarthritis was induced in adult male Sprague-Dawley rats (250-300 g) via intraarticular injection of complete Freund's adjuvant (CFA) into the tibiotarsal joint. Animals were irradiated 72 h after CFA administration with a 780 nm GaAlAs laser at 4.5 J/cm2 (30 mW, 30 sec/spot) and 72 J/cm2 (80 mW, 180 sec/spot) daily for 10 days. After LLLT, the animals were euthanized and their arthritic ankles were collected for histopathological analysis, immunoassays of tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)3 and 5B5, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: LLLT at a fluence of 4.5 J/cm2 significantly reduced infiltration of inflammatory cells and expressions of TNF-α-, MMP3- and 5B5-like immunoreactivities, as well as resulting in more TUNEL-positive apoptotic cells in the synovium. No significant changes were observed in these biochemicals and inflammation in arthritic animals treated with 72 J/cm2. CONCLUSIONS: LLLT with low fluence is highly effective in reducing inflammation to sites of injury by decreasing the numbers of FLS, inflammatory cells, and mediators in the CFA-induced arthritic model. These data will be of value in designing clinical trials of LLLT for RA.

Remote dose-dependent effects of dry needling at distant myofascial trigger spots of rabbit skeletal muscles on reduction of substance P levels of proximal muscle and spinal cords.

BACKGROUND: Dry needling at distant myofascial trigger points is an effective pain management in patients with myofascial pain. However, the biochemical effects of remote dry needling are not well understood. This study evaluates the remote effects of dry needling with different dosages on the expressions of substance P (SP) in the proximal muscle, spinal dorsal horns of rabbits. METHODS: Male New Zealand rabbits (2.5-3.0 kg) received dry needling at myofascial trigger spots of a gastrocnemius (distant muscle) in one (1D) or five sessions (5D). Bilateral biceps femoris (proximal muscles) and superficial laminaes of L5-S2, T2-T5, and C2-C5 were sampled immediately and 5 days after dry needling to determine the levels of SP using immunohistochemistry and western blot. RESULTS: Immediately after dry needling for 1D and 5D, the expressions of SP were significantly decreased in ipsilateral biceps femoris and bilateral spinal superficial laminaes (P < .05). Five days after dry needling, these reduced immunoactivities of SP were found only in animals receiving 5D dry needling (P < .05). CONCLUSIONS: This remote effect of dry needling involves the reduction of SP levels in proximal muscle and spinal superficial laminaes, which may be closely associated with the control of myofascial pain.

Low-level laser therapy alleviates neuropathic pain and promotes function recovery in rats with chronic constriction injury: possible involvements in hypoxia-inducible factor 1α (HIF-1α).

Nerve inflammation plays an important role in the development and progression of neuropathic pain after chronic constrictive injury (CCI). Recent studies have indicated that hypoxia-inducible factor 1α (HIF-1α) is crucial in inflammation. Low-level laser therapy has been used in treating musculoskeletal pain, but rare data directly support its use for neuropathic pain. We investigated the effects of low-level laser on the accumulation of HIF-1α, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in controlling neuropathic pain, as well as on the activation of vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) in promoting functional recovery in a rat CCI model. CCI was induced by placing four loose ligatures around the sciatic nerve of rats. Treatments of low-level laser (660 nm, 9 J/cm(2)) or sham irradiation (0 J/cm(2)) were performed at the CCI sites for 7 consecutive days. The effects of laser in animals with CCI were determined by measuring the mechanical paw withdrawal threshold, as well as the sciatic, tibial, and peroneal function indices. Histopathological and immunoassay analyses were also performed. Low-level laser therapy significantly improved paw withdrawal threshold and the sciatic, tibial, and peroneal functional indices after CCI. The therapy also significantly reduced the overexpressions of HIF-1α, TNF-α, and IL-1ß, and increased the amounts of VEGF, NGF, and S100 proteins. In conclusion, a low-level laser could modulate HIF-1α activity. Moreover, it may also be used as a novel and clinically applicable therapeutic approach for the improvement of tissue hypoxia/ischemia and inflammation in nerve entrapment neuropathy, as well as for the promotion of nerve regeneration. These findings might lead to a sufficient morphological and functional recovery of the peripheral nerve.

Dry needling at myofascial trigger spots of rabbit skeletal muscles modulates the biochemicals associated with pain, inflammation, and hypoxia.

Background and Purpose. Dry needling is an effective therapy for the treatment of pain associated with myofascial trigger point (MTrP). However, the biochemical effects of dry needling that are associated with pain, inflammation, and hypoxia are unclear. This study investigated the activities of ß-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF after different dosages of dry needling at the myofascial trigger spots (MTrSs) of a skeletal muscle in rabbit. Materials and Methods. Dry needling was performed either with one dosage (1D) or five dosages (5D) into the biceps femoris with MTrSs in New Zealand rabbits. Biceps femoris, serum, and dorsal root ganglion (DRG) were sampled immediately and 5 d after dry needling for ß-endorphin, substance P, TNF-α, COX-2, HIF-1α, iNOS, and VEGF immunoassays. Results. The 1D treatment enhanced the ß-endorphin levels in the biceps femoris and serum and reduced substance P in the biceps femoris and DRG. The 5D treatment reversed these effects and was accompanied by increase of TNF-α, COX-2, HIF-1α, iNOS, and VEGF production in the biceps femoris. Moreover, the higher levels of these biochemicals were still maintained 5 d after treatment. Conclusion. Dry needling at the MTrSs modulates various biochemicals associated with pain, inflammation, and hypoxia in a dose-dependent manner.