Ameliorative effects of escin on neuropathic pain induced by chronic constriction injury of sciatic nerve.

ETHNOPHARMACOLOGY RELEVANCE: Escin is a natural mixture of triterpene saponins extracted from the seeds of Aesculus wilsonii Rehd. And has been reported to possess the therapeutic effects against neuropathic pain (NP). However, the underlying mechanisms remain unclear. AIM OF THE STUDY: The present study aimed to investigate the therapeutic effects and explore the underlying mechanisms of escin on rats of NP induced by chronic constriction injury (CCI) of sciatic nerve. MATERIALS AND METHODS: Rats were treated with escin (7, 14, and 28 mg/kg, i. g.) daily from the third day after the surgery (day 0) for consecutive 14 days. Regular behavior and thermal threshold were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of inflammatory factors and biochemical factors in dorsal root ganglion (DRG). Inflammatory pain responses and nerve injuries were induced by the CCI model. Tonic pain model and acute inflammatory model induced by formalin or carrageenan were established to evaluated the pharmacological effects of escin on acute inflammatory pain. Corresponding behaviors were monitored and relevant gene expression such as c-fos, mu opioid receptor (MOR) and KCNK1 were detected by qRT-PCR. Investigate the neuroprotective effects of escin on PC12 cell injury induced by lipopolysaccharide (LPS). Cell morphology was observed under inverted microscope and neuroprotective effect of escin on cell activity was assessed by MTT assay. RESULTS: Escin could widen thermal threshold, downregulate the concentration of inflammatory factors like tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, suppress the gene expression of toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), decrease the level of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) remarkably. In addition, escin significantly lowered the duration of licking, numbers of flinches and increase in paw edema, showing great therapeutic effects on inflammatory pain responses. Moreover, the activity of injured PC12 cells was significantly improved after escin administrated. CONCLUSION: Escin exerted the ameliorative effects on NP induced by CCI which may be related to downregulating the release of pro-inflammatory cytokines, suppressing TLR-4/NF-κB signal pathway, thereafter decreasing the level of GFAP and NGF.

Changes in resting-state functional connectivity in nonacute sciatica with acupuncture modulation: A preliminary study.

AIMS: To investigate the functional connectivity (FC) in nonacute sciatica and the neuronal correlation of acupuncture analgesia. METHODS: A prospective study employing resting-state functional magnetic resonance imaging was conducted. Twelve sciatica patients were enrolled to receive six or 18 acupoints of acupuncture treatment twice a week for 4 weeks. Regional homogeneity (ReHo) and seed-based FC were performed. RESULTS: Regional homogeneity analysis demonstrated a greater alteration in the right posterior cingulate cortex (PCC) during the pre-acupuncture phase than during the postacupuncture phase. Compared to that of healthy controls, the PCC-seeded FC (default mode network, DMN) of sciatica patients exhibited hyperconnectivity of PCC-FC with the PCC-bilateral insula, cerebellum, inferior parietal lobule, right medial prefrontal cortex, and dorsal anterior cingulate cortex during the pre-acupuncture phase as well as hypoconnectivity of PCC-FC with the right cerebellum, left precuneus, and left dorsal medial prefrontal cortex during the postacupuncture phase. Correlation analysis between PCC-seeded FC and behavior measurements revealed a positive association with the duration of sciatica in the right inferior parietal lobule prior to acupuncture treatment. CONCLUSIONS: Acupuncture in chronic sciatica patients is associated with normalized DMN activity and modulation of descending pain processing. The changes in the subclinical endophenotype of brain FC after acupuncture treatment may provide clues for understanding the mechanism of acupuncture-mediated analgesia in chronic pain.

Shear Wave Elastographic Investigation of the Immediate Effects of Slump Neurodynamics in People With Sciatica.

OBJECTIVES: Neurodynamic techniques are often used to treat people with sciatica pain, but their mechanical effects on the sciatic nerve are unknown. Shear wave elastography (SWE) has been shown to effectively estimate the stiffness of peripheral nerves in real time. The aim of this study was to use SWE to assess the effects of slump neurodynamics in the sciatic stiffness of people with sciatica. METHODS: Sixteen participants volunteered for this study. The sciatic stiffness of 8 patients with unilateral chronic sciatica and 8 healthy control participants was measured by SWE, with the participants in a prone position and during a dynamic condition (ie, ankle dorsiflexion). These measurements were performed before and immediately after the neurodynamic intervention, which consisted of a static slump position applied to the symptomatic limb of the patients with sciatica and in a randomly chosen limb of the healthy participants. RESULTS: The 8 patients with sciatica included 6 male and 2 female patients, and the 8 healthy control participants included 5 male and 3 female volunteers. Slump neurodynamics resulted in an immediate decrease in the sciatic nerve stiffness of the symptomatic limb in people with sciatica by 16.1% (effect size = 0.65; P = .019). The intervention showed no significant changes in the sciatic nerve stiffness of the healthy participants (effect size = 0.05; P = .754). CONCLUSIONS: Slump neurodynamics have the potential of decreasing the sciatic nerve stiffness in people with sciatica, and this effect can be quantified by SWE, which may provide valuable information for health professionals.

The ambiguity of sciatica as a clinical diagnosis: A case series.

Sciatica as a clinical diagnosis is nonspecific. A diagnosis of sciatica is typically used as a synonym for lumbosacral radiculopathy. However, the differential for combined low back and leg pain is broad, and the etiology can be one several different conditions. The lifetime prevalence of sciatica ranges from 12.2% to 43%, and nonsuccessful outcomes of treatment are prevalent. Nurse practitioners and other primary care clinicians often have minimal training in differential diagnosis of the complex causes of lower back and leg pain, and many lack adequate time per patient encounter to work up these conditions. Differentiating causes of low back and leg pain proves challenging, and inadequate or incomplete diagnoses result in suboptimal outcomes. Chiropractic care availability may lessen demands of primary care with respect to spinal complaints, while simultaneously improving patient outcomes. The authors describe three patients referred from primary care with a clinical diagnosis of sciatica despite differing underlying pathologies. More precise clinical terminology should be used when diagnosing patients with combined low back and leg pain. Nurse practitioners and other clinicians' triage, treat, and determine appropriate referrals for low back and leg pain. Multidisciplinary care including chiropractic may add value in settings where patients with lower back and leg pain are treated.

Pragmatic neural tissue management improves short-term pain and disability in patients with sciatica: a single-arm clinical trial.

Objectives: To evaluate the clinical effect of sciatic neural mobilization in combination with the treatment of surrounding structures for sciatica patients. Secondly, we were also interested in identifying possible baseline characteristics that may be associated with improvements in pain and disability for sciatica patients. Methods: Twenty-eight patients with a clinical diagnosis of sciatica were treated with neural mobilization, joint mobilization and soft tissue techniques. Pain intensity and lumbar disability were assessed at baseline and after treatment using a Numerical Rating Scale (0-10) and the Oswestry Disability Index (0-100), respectively. The pre- and post-intervention data were compared. The research protocol was registered under the number NCT03663842. Results: Participants attended an average of 16 (SD±5.6) treatmentsessions over an average of 12 weeks. Decrease in pain scores (before median = 8, after median = 2; p < 0.001) and improvement in lumbar disability scores (before median = 33.3%, after median = 15.6%; p < 0.001) were observed. A multiple linear regression analysis showed that duration of pain and age of the patient predicted the disability improvement: F (2, 24) = 4.084, p < 0.030, R2 = 0.254. Discussion: Patients with sciatica may benefit from neural mobilization in combination with manual therapy for pain and lumbar disability. Longer pain duration and younger age had a negative influence on lumbar disability improvement.

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.

OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.

Effect and neurophysiological mechanism of acupuncture in patients with chronic sciatica: protocol for a randomized, patient-assessor blind, sham-controlled clinical trial.

BACKGROUND: Sciatica is a relatively frequent illness that easily becomes a chronic and relapsing condition. Although numerous systematic reviews have analyzed various therapies for sciatica, the validity of their included studies is limited. Considering the limitations of conventional treatment options for sciatica, acupuncture is a possible option; however, evidence supporting its efficacy and mechanism in patients with sciatica is lacking. The aim of this proposed protocol is to investigate the effect and neurophysiological mechanism of acupuncture in patients with chronic sciatica. METHODS/DESIGN: This study is a randomized, patient-assessor blind, two-arm, parallel, non-penetrating, sham-controlled clinical trial. Eligible participants will include adults (aged 19-70 years old) with a clinical diagnosis of chronic sciatica (40 mm or more of a 100-mm visual analog scale (VAS) for bothersomeness) blinded to the treatment received. Patients will be randomly allocated into the acupuncture treatment group (manual acupuncture plus electroacupuncture (EA), n = 34) or the sham acupuncture control group (sham acupuncture plus placebo EA without electrical stimulation, n = 34). Groups will receive treatment twice a week for a total of eight sessions over 4 weeks. Functional magnetic resonance imaging will be implemented at baseline and endpoint to investigate the mechanism of acupuncture. The primary outcome measure is the VAS for bothersomeness and secondary outcomes include the VAS for pain intensity, Oswestry Disability Index, EuroQol 5-Dimension, Coping Strategy Questionnaire, Beck's Depression Inventory, and State-Trait Anxiety Inventory. Adverse events will be assessed at every visit. DISCUSSION: The results of this trial (which will be available in 2020) should provide important clinical evidence for the effect of acupuncture and demonstrate how acupuncture can be helpful for the treatment of chronic sciatica. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03350789 . Registered on 15 November 2017.

Effects of a water extract of Lepidium meyenii root in different models of persistent pain in rats.

Lepidium meyenii (Walp.), commonly called maca, is an Andean crop belonging to the Brassicaceae family. Maca hypocotils are habitually consumed as customary food as well as traditional remedies for pathological conditions such as infertility. Moreover, the characterization of maca extracts revealed the presence of compounds that are able to modulate the nervous system. Aimed to evaluate the efficacy of L. meyenii in persistent pain, the present study analyzed the effects of a commercial root extract from maca in different animal models reproducing the most common causes of chronic painful pathologies. A qualitative characterization of this commercial extract by high performance liquid chromatography-mass spectrometry and tandem mass spectrometry analyses allowed us to confirm the presence of some macamides known as bioactive constituents of this root and the absence of the main aromatic glucosinolates. The acute oral administration of maca extract is able to reduce mechanical hypersensitivity and postural unbalance induced by the intra-articular injection of monoiodoacetate and the chronic-constriction injury of the sciatic nerve. Furthermore, L. meyenii extract reverts pain threshold alterations evoked by oxaliplatin and paclitaxel. A good safety profile in mice and rats was shown. In conclusion, the present maca extract could be considered as a therapeutic opportunity to relieve articular and neuropathic pain.

Immediate relief of herniated lumbar disc-related sciatica by ankle acupuncture: A study protocol for a randomized controlled clinical trial.

BACKGROUND: Around 90% of sciatica cases are due to a herniated intervertebral disc in the lumbar region. Ankle acupuncture (AA) has been reported to be effective in the treatment of acute nonspecific low back pain. This study aims to evaluate the efficacy of a single session of ankle acupuncture for disc-related sciatica. METHOD: This will be a double-blinded, randomized controlled clinical trial. Patients diagnosed with disc-related sciatica will be randomly divided into 3 parallel groups. The treatment group (n = 30) will receive ankle acupuncture. The 2 control groups will either undergo traditional needle manipulation (n = 30) or sham acupuncture (n = 30) at the same point as the treatment group. The primary outcome will be pain intensity on a visual analog scale (VAS). The secondary outcomes will be paresthesia intensity on a VAS and the Abbreviated Acceptability Rating Profile (AAPR). The success of blinding will be evaluated, and the needle-induced sensation and adverse events will be recorded. All outcomes will be evaluated before, during, and after the treatment. DISCUSSION: This study will determine the immediate effect and specificity of ankle acupuncture for the treatment of disc-related sciatica. We anticipate that ankle acupuncture might be more effective than traditional needle manipulation or sham acupuncture. TRIAL REGISTRATION: ChiCTR-IPR-15007127 (http://www.chictr.org.cn/showprojen.aspx?proj=11989).

Auricular acupuncture diagnosis in patients with lumbar hernia.

BACKGROUND: Auricular Acupuncture Diagnosis is a diagnostic method which is essential for the topographic identification on the auricle of the anatomical parts of the body carrying a particular ailment or dysfunction. OBJECTIVE: To identify the specific zones related to lumbar hernia in patients treated with a series of epidural infiltrations with corticosteroids. METHODS: In a consecutive group of thirty patients with lumbar hernia 2 diagnostic methods used in Auricular Acupuncture Diagnosis, Pain Pressure Test and Electric Skin Resistance Test, were applied before the first infiltration (T0), before the second and the third infiltration (T1, T2) and one week after the third infiltration (T3). The parameters, whose variations were analyzed at T0-T3, were the following: the number of points identified; the intensity of pain on a verbal rating scale and the foot-hand distance in cm with bent spine and extended knees. The identified points were reported on the Auricular Sectogram which is a validated graphic system suitable for a correct transcription of the points and indicated for a statistical analysis of their distribution on the different sectors. RESULTS: A significant association was found for some auricular areas, along the series of epidural infiltrations, with a progressive reduction in the number of tender and low electrical resistance points together with a decrease of pain and hand-foot distance. CONCLUSIONS: The auricular zones found with Auricular Acupuncture Diagnosis in our group of patients seem of clinical relevance and could be included in the complementary treatment of lumbar-sciatic pain in lumbar hernia.

Onset and maximum values of electromyographic amplitude during prone hip extension after neurodynamic technique in patients with lumbosciatic pain: A pilot study.

OBJECTIVE: The mechanisms underlying the effects of neurodynamic techniques are still unknown. Therefore, the aim of this study was to provide a starting point for future research on explaining why neurodynamic techniques affect muscular activities in patients with sciatic pain. METHODS: A double-blind trial was conducted in 12 patients with lumbosciatica. Surface electromyography activity was assessed for different muscles during prone hip extension. Pre- and post-intervention values for muscle activity onset and maximal amplitude signals were determined. RESULTS: There was a significant reduction in the surface electromyography activity of maximal amplitude in the erector spinae and contralateral erector spinae (p < 0.05). Additionally, gluteus maximus (p < 0.05) activity onset was delayed post-intervention. CONCLUSIONS: Self-neurodynamic sliding techniques modify muscular activity and onset during prone hip extension, possibly reducing unnecessary adaptations for protecting injured components. Future work will analyze the effects of self-neurodynamic sliding techniques during other physical tasks.

[A Randomized Controlled Clinical Trial of Treatment of Lumbar Disc Herniation-induced Sciatica by Acupuncture Stimulation of Sciatic Nerve Trunk].

OBJECTIVE: To observe the efficacy of acupuncture stimulation of the sciatic nerve trunk in the treatment of patients suffering from sciatica induced by lumbar disc herniation (LDH). METHODS: A total of 60 LDH sciatica patients met the inclusion criteria were randomly divided into treatment group and control group, with 30 cases in each. Patients of the treatment group were treated by directly needling the sciatic nerve and routine acupuncture of Ashi-points, Lumbar Jiaji (EX-B 2), Dachangshu (BL 28), etc., and those of the control group treated by simple routine acupuncture. The treatment was conducted once a day, 5 times a week, 4 weeks altogether. The clinical effect was evaluated according to the "Standards for Diagnosis and Therapeutic Effect Evaluation of Syndromes of Chinese Medicine" and the pain intensity was assessed by using simplified Short-Form McGill Pain Questionnaire (SF-MPQ) containing pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI). RESULTS: After the treatment, of the two 30 cases of LDH sciatica patients in the control and treatment groups, 11 and 18 were cured, 7 and 7 experienced marked improvement, 10 and 4 were effective, 2 and 1 was invalid, with the effective rate being 93.3% and 96.7%, respectively. The cured+markedly effective rate of the treatment group was significantly higher than that of the control group (P<0.05, 83.3% vs 60.0%). Compared with pre-treatment, the scores of PRI, VAS and PPI were evidently lowered in both groups (P<0.01), and the effect of the treatment group was notably better than that of the control group (P<0.01). CONCLUSIONS: Acupuncture stimulation of the sciatic nerve trunk is effective in relieving sciatica in LDH patients, and is superior to simple routine acupuncture in the clinical efficacy.

Effects of Shinbaro pharmacopuncture in sciatic pain patients with lumbar disc herniation: study protocol for a randomized controlled trial.

BACKGROUND: Lumbar disc herniation is a major cause of sciatica and low back pain and imposes a heavy burden on both individual and society. While use of pharmacopuncture, a combined form of acupuncture and herbal medicine, for lumbar disc herniation is widespread in Korea and China, there is a paucity of research. METHODS/DESIGN: This study is the protocol for a three-armed, randomized, patient, physician, and assessor-blinded controlled pilot study. Sixty patients with severe non-acute sciatic pain diagnosed with lumbar disc herniation (NRS ≥ 5, onset between 4 weeks and 6 months) will be recruited and randomized 20 each to the Shinbaro pharmacopuncture (pharmacopuncture with acupuncture), acupuncture, and usual care groups, respectively. The 2 acupuncture groups will receive 2 sessions/week of acupuncture alone or with pharmacopuncture for 4 weeks (total 8 sessions), and the usual care group will receive conventional medication 2-3 times/day and physical therapy 2 sessions/week over 4 weeks (total 8 sessions). The initial acupuncture physician will administer acupuncture at 5 acupoints (GB30, BL40, BL25, BL23, GB34) in the 2 acupuncture groups, and mark an additional acupoint. A second acupuncture physician will administer pharmacopuncture to the marked acupoint in the pharmacopuncture group, and acupuncture in the acupuncture group during acupuncture needle retention. The second physician will administer acupuncture and pharmacopuncture in a similar manner in terms of advice and manual stimulation to maintain patient-blinding, treat the patient out of view of the initial physician, remove the additional acupuncture needle immediately, and cover the area with adhesive bandage to maintain physician-blinding. The primary endpoint will be at 5 weeks post-randomization, and the primary outcome will be Visual Analog Scale (VAS) of sciatic pain. Secondary outcomes will be VAS of low back pain, Numeric Rating Scale (NRS) of low back pain and sciatic pain, ODI, SF-36, EQ-5D, and PGIC. Post-treatment evaluations will take place 5, 7, 9, and 12 weeks after randomization. DISCUSSION: This trial will evaluate the comparative clinical effectiveness of pharmacopuncture for severe non-acute sciatic pain patients diagnosed with lumbar disc herniation with usual care of conventional medicine and that of Korean medicine (acupuncture), monitor its safety, and serve as basis for a large-scale, multicenter trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02384928 , registered 27 February 2015.

Validation and Test-Retest Reliability of New Thermographic Technique Called Thermovision Technique of Dry Needling for Gluteus Minimus Trigger Points in Sciatica Subjects and TrPs-Negative Healthy Volunteers.

The aim of this study was to assess the validity and test-retest reliability of Thermovision Technique of Dry Needling (TTDN) for the gluteus minimus muscle. TTDN is a new thermography approach used to support trigger points (TrPs) diagnostic criteria by presence of short-term vasomotor reactions occurring in the area where TrPs refer pain. Method. Thirty chronic sciatica patients (n=15 TrP-positive and n=15 TrPs-negative) and 15 healthy volunteers were evaluated by TTDN three times during two consecutive days based on TrPs of the gluteus minimus muscle confirmed additionally by referred pain presence. TTDN employs average temperature (T avr), maximum temperature (T max), low/high isothermal-area, and autonomic referred pain phenomenon (AURP) that reflects vasodilatation/vasoconstriction. Validity and test-retest reliability were assessed concurrently. Results. Two components of TTDN validity and reliability, T avr and AURP, had almost perfect agreement according to κ (e.g., thigh: 0.880 and 0.938; calf: 0.902 and 0.956, resp.). The sensitivity for T avr, T max, AURP, and high isothermal-area was 100% for everyone, but specificity of 100% was for T avr and AURP only. Conclusion. TTDN is a valid and reliable method for T avr and AURP measurement to support TrPs diagnostic criteria for the gluteus minimus muscle when digitally evoked referred pain pattern is present.

Intensive vasodilatation in the sciatic pain area after dry needling.

BACKGROUND: Short-term vasodilatation in the pain area after dry needling (DN) of active trigger points (TrPs) was recorded in several cases of sciatica. Moreover, the presence of TrPs in sciatica patients secondary to primary lesion was suggested. Still, it is not known how often they occur and if every TrPs can provoke vasomotor reactions. The purpose of this study was to evaluate the prevalence of active TrPs among subacute sciatica patients and the response to DN under infrared thermovision (IRT) camera control. METHOD: Fifty consecutive Caucasian patients (mean age 41.2 ± 9.1y) with subacute sciatica were diagnosed towards gluteus minimus TrPs co-existence. Based on TrPs confirmation, patients were divided into two groups: TrPs-positive and TrPs-negative, than DN under IRT control was performed. Skin temperature changes and the percentage size of vasomotor reactions in the pain area were evaluated if present. RESULTS: The prevalence of active TrPs was 32.0%. Every TrPs-positive presented vasodilatation dependent on TrPs co-diagnosis (r = 0.72 p < 0.000) and pain recognition during DN (r = 0.4 p < 0.05). The size of vasodilatation in TrPs-positive subjects was: post-DN 12.3 ± 4.0% and post-observation 22.1 ± 6.1% (both p = 0.000) versus TrPs-negative: post-DN 0.4 ± 0.3% and post-observation 0.4 ± 0.2%. A significant temperature increase in the thigh and calf was confirmed for TrPs-positive subjects only (both p < 0.05). Post-DN and post-observation temperatures were as follows: average (thigh:1.2 ± 0.2°C; 1.4 ± 0.2°C, both p < 0.05 and calf: 0.4 ± 0.2°C; 0.4 ± 0.3°C, both p < 0.05) and maximum (thigh 1.4 ± 0.3°C 1.6 ± 0.3°C; both p < 0.05). CONCLUSIONS: The presence of active TrPs within the gluteus minimus muscle among subacute sciatica subjects was confirmed. Every TrPs-positive sciatica patient presented DN related vasodilatation in the area of referred pain. The presence of vasodilatation suggests the involvement of sympathetic nerve activity in myofascial pain pathomechanism. Although the clinical meaning of TrPs in subacute sciatica patients is possible, further studies on a bigger group of patients are still required. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001060639. Registered 3 October 2014.

Intrathecal ultra-low dose naloxone enhances the antihyperalgesic effects of morphine and attenuates tumor necrosis factor-α and tumor necrosis factor-α receptor 1 expression in the dorsal horn of rats with partial sciatic nerve transection.

BACKGROUND: Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. We designed this investigation to examine whether ultra-low dose naloxone administered alone or in combination with morphine could alter the concentration of the excitatory amino acids (EAAs) glutamate and aspartate, as well as the expression of tumor necrosis factor-α (TNF-α) and its receptors (TNFR1 and TNFR2) in the spinal cord dorsal horn of rats with partial sciatic nerve transection (PST). METHODS: Male Wistar rats underwent intrathecal catheter implantation for drug delivery and were divided in 7 groups: sham-operated + saline (sham), PST + saline (S), PST + 15 ng naloxone (n), PST + 15 µg naloxone (N), PST + 10 µg morphine (M), PST + 15 ng naloxone + 10 µg morphine (Mn), PST + 15 µg naloxone + 10 µg morphine (MN). Thermal withdrawal latency and mechanical withdrawal threshold, TNF-α and TNFR expression in the spinal cord and dorsal root ganglia, and EAAs glutamate and aspartate concentration in cerebrospinal fluid dialysates were measured. RESULTS: Ten days after PST, rats developed hyperalgesia (P < 0.0001) and allodynia (P < 0.0001), and increased TNF-α (P < 0.0001) and TNFR1 expression (P = 0.0009) were measured in the ipsilateral spinal cord dorsal horn. The antihyperalgesic and antiallodynic effects of morphine (10 µg) were abolished by high-dose naloxone (15 µg; P = 0.0031) but enhanced by ultra-low dose naloxone (15 ng; P = 0.0015), and this was associated with a reduction of TNF-α (P < 0.0001) and TNFR1 (P = 0.0009) expression in the spinal cord dorsal horn and EAAs concentration (glutamate: P = 0.0001; aspartate: P = 0.004) in cerebrospinal fluid dialysate. Analysis of variance (ANOVA) or Student t test with Bonferroni correction were used for statistical analysis. CONCLUSIONS: Ultra-low dose naloxone enhances the antihyperalgesia and antiallodynia effects of morphine in PST rats, possibly by reducing TNF-α and TNFR1 expression, and EAAs concentrations in the spinal dorsal horn. Ultra-low dose naloxone may be a useful adjuvant for increasing the analgesic effect of morphine in neuropathic pain conditions.

The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica.

BACKGROUND: Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. AIM: This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. METHODS/RESULTS: Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin. CONCLUSIONS: It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.

[Effects of acupuncture on default mode network images of chronic sciatica patients in the resting network state].

OBJECTIVE: To observe the functional magnetic resonance imaging (fMRI) data changes of default mode network (DMN) in chronic sciatica patients in the resting network state treated by acupuncture, and to study the correlation between DMN and the consisting effects after acupuncture analgesia. METHODS: Weizhong (BL40) and Huantiao (GB30) of the patients' lower limbs were selected as the main points to acupuncture for ten times. The whole brain was scanned using fMRI. The independent component analysis (ICA) was adopted to get DMN information. The brain DMN function link was analyzed in the two groups of subjects. RESULTS: The DMN images were obtained in all subjects after DMN fMRI data processing. The main DMN differences between the sciatica patients group and the healthy control group were demonstrated as decreased activities of DLPFC and anterior cingulate cortex (ACC). After acupuncture, activities of these regions basically recovered to normal. The DMN of healthy volunteers shown by fMRI data in the RNS mainly existed in the precuneus, BA7, BA10, and ACC. CONCLUSION: MRI images of DMN in the RNS could reflect chronic pain, which was suitable for studies on the effects after acupuncture analgesia.

The warming acupuncture for treatment of sciatica in 30 cases.

OBJECTIVE: To observe the relation between the pain threshold and the therapeutic effects of acupuncture for sciatica. METHODS: 90 sciatica patients were equally divided at random into the following 3 groups: a warming acupuncture group treated with the needles warmed by burning moxa, a western medicine group administered Nimesulide tablets and a point-injection group with Anisodamine injected. The pain threshold was tested before treatment and after the first, second and third treatment courses. RESULTS: The warming acupuncture therapy showed better therapeutic effects than the other two groups with significant differences in the change of pain threshold and the improvement of clinical symptoms and signs (P<0.01). CONCLUSION: Acupuncture can relieve the symptoms of sciatica with the increase of pain threshold.