Effect of Ropivacaine-Loaded Magnetic Nanoparticles on Ankle Nerve Block in Rats

Aim. Our study is to determine the influence of ropivacaine-loaded magnetic nanoparticles (MNP/Rop) on ankle nerve block in rats. Materials and Methods. MNP/Rop was prepared and then injected intravenously into rats to evaluate its anesthetic effect on rat limbs. Mechanical pain thresholds paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWL) were employed for the assessment of ankle nerve block in rats. Results. PWT increased from T1 to T4 in each group ( P < 0.05 ). The intergroup comparison determined no distinct difference in the PWT value among the three series at T1 ( P > 0.05 ); however, PWT values at T2-T4 were higher in nerve block control group (NBCG) and MNP/Rop group than in blank group (BG), and they remained slightly higher in MNP/Rop group than in NBCG. The intragroup comparison revealed that from T1 to T4, PWL in each group showed a rising trend. The PWL at T1 showed no evident difference among the three series ( P > 0.05 ); however, PWL values at T2-T4 were higher in NBCG and MNP/Rop group than in BG, and they remained slightly higher in MNP/Rop group than in NBCG. In MNP/Rop group, both PWT and PWL increased with the increase of Fe3O4 load in MNP/Rop ( P < 0.05 ), while PWT and PWL remained unchanged when the load was 2.189%; moreover, PWT and PWL elevated as Rop concentration increased in MNP/Rop ( P < 0.05 ), while they kept unaltered under 40 μL 1% Rop. Conclusion. Intravenous injection of MNP/Rop into rats and inhalation of MNP into the ankle joint can effectively block ankle nerve conduction in rats.

Modulatory Effect of Probiotic Lactobacillus rhamnosus PB01 on Mechanical Sensitivity in a Female Diet-Induced Obesity Model

Obese animals and humans demonstrate higher sensitivity to pain stimuli. Among the endogenous factors prompting obesity, the intestinal microbiota has been proposed to influence responsiveness to pain. The beneficial effects of probiotics on obesity are well documented, whereas data on their analgesic efficacy is minimal. The protective effect of probiotics on nociception in diet-induced obese male mice has been previously demonstrated, but the sex differences in pain sensitivity and analgesic response do not allow for the generalization of these findings to the female gender. Hence, this study aimed at investigating the potential effects of oral probiotic supplementation on mechanical pain thresholds in female diet-induced obese mice compared with controls. Thirty-two adult female mice ( N = 32 ) were randomly divided into two groups receiving standard (normal-weight group; NW) or high-fat diet (diet-induced obesity; DIO). All rats received a single daily dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) for four weeks by gavage. Mechanical pain thresholds were recorded by an electronic von Frey device at baseline, at the end of weeks 2, 4, 6, and 8 in both DIO and NW groups with and without consumption of probiotics. Blood samples were obtained for the measurement of lipid profile and reproductive hormone levels. Bodyweight was considerably lower ( P < 0.001 ) in groups supplied with probiotics than groups without probiotics. Pressure pain threshold values showed a significant ( P < 0.001 ) increase (reduced pain sensitivity) following probiotic supplementation, proposing a modulatory effect of probiotics on mechanical sensory circuits and mechanical sensitivity, which might be a direct consequence of weight loss or an indirect result of the probiotics’ anti-inflammatory properties. Understanding the precise underlying mechanism for the effect of probiotics on weight loss and mechanical pain sensitivity seen in this study warrants further investigation.

Sympathetic and sensory nerve fiber function in multiple system atrophy and idiopathic Parkinson’s disease

Objective To explore small fiber somatosensory and sympathetic function in PD and MSA. Methods We recruited 20 PD patients (7 women, median age 65.5 years; IQR 54.75–70.0), 10 MSA patients (4 women; median age 68 years; IQR 66.25–74.0), and 10 healthy subjects (HC; 4 women, median age 68; IQR 59.0–71.0 years). Autonomic testing included forehead cooling, intradermal microdialysis of norepinephrine (NE; 10–5; 10–6; 10–7; and 10–8), and orthostatic hypotension (OH); somatosensory testing included quantitative sensory testing (QST) according to the protocol of the German Research Network on Neuropathic Pain (DFNS). Results OH occurred more frequently in PD (p = 0.018) and MSA (p = 0.002) compared to HC. Vasoconstriction responses were stronger in PD compared to MSA during forehead cooling (p = 0.044) and microdialysis of physiologically concentrated NE solutions (10–7; 10–8; p = 0.017). PD and MSA had impaired cold (PD: p < 0.01; MSA: p < 0.05) and warm detection thresholds (PD and MSA, both p < 0.05). The mechanical detection threshold was higher in PD (p < 0.01). Conversely, mechanical pain thresholds were decreased in PD and MSA (both p < 0.001), indicating mechanical hyperalgesia. Conclusion In contrast to MSA, we found evidence of peripheral adrenoreceptor hypersensitivity in PD, probably caused by peripheral sympathetic denervation. Sensory testing revealed peripheral neuropathy and central pain sensitization in PD and MSA. Jointly, our data demonstrate autonomic and somatosensory dysfunction in PD and MSA.

Reversal of hyperactive subthalamic circuits differentially mitigates pain hypersensitivity phenotypes in parkinsonian mice

Although pain is a prevalent nonmotor symptom in Parkinson’s disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.

Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points

The aim of this study was to determine the effects of acupotomy on energy crises in rat trigger points (TrPs) by measuring mechanical pain thresholds (MPTs) and levels of acetylcholinesterase (AChE), free sarcoplasmic calcium (Ca2+), adenosine 5′-triphosphate (ATP), adenosine 5′-monophosphate (AMP), substance P (SP), and calcitonin gene-related peptide (CGRP) in rat muscle TrP tissue. Male Sprague Dawley rats (n = 32) were randomly divided into four groups: control, TrP, acupotomy, and lidocaine injection. Enzyme-linked immunosorbent assays were used to measure AChE, and free sarcoplasmic Ca2+ concentrations were determined by fluorescent staining with Fura-2 AM; high-performance liquid chromatography was used to measure ATP and AMP, and SP and CGRP were evaluated by immunohistochemistry. Compared with the control group, free sarcoplasmic Ca2+, AMP, SP, and CGRP were higher in the model group, while MPT, AChE, and ATP were lower. Treatment with acupotomy or lidocaine injection reduced free sarcoplasmic Ca2+, SP, and CGRP and increased MPTs and AChE levels compared with the model group. However, only acupotomy also led to decreased AMP and increased ATP levels relative to the model group. We conclude that acupotomy can alleviate energy crises at TrPs.

Regulatory Effects of Propofol on High-Dose Remifentanil-Induced Hyperalgesia

We aimed to evaluate the regulatory effects of propofol on high-dose remifentanil-induced hyperalgesia. A total of 180 patients receiving laparoscopic cholecystectomy were randomly divided into sevoflurane + high-dose remifentanil (SH) group, sevoflurane + low-dose remifentanil (SL) group and propofol + high-dose remifentanil group (PH) group (n=60). After intravenous administration of midazolam, SH and SL groups were induced with sevoflurane and remifentanil, and PH group was induced with propofol and remifentanil. During anesthesia maintenance, SH and SL groups were given 0.3 μg/kg/min and 0.1 μg/kg/min sevoflurane and remifentanil respectively, and PH group was given 0.3 μg/kg/min propofol and remifentanil. The three groups had significantly different awakening time, extubation time and total dose of remifentanil (P<0.001). Compared with SL group, periumbilical mechanical pain thresholds 6 h and 24 h after surgery significantly decreased in SH group (P<0.05), and the visual analog scale (VAS) scores significantly increased 30 min, 2 h and 6 h after surgery (P<0.05). Compared with SH group, periumbilical mechanical thresholds 6 h and 24 h after surgery were significantly higher in PH group (P<0.05), and VAS scores 30 min, 2 h and 6 h after surgery were significantly lower (P<0.05). PH group first used patient-controlled intravenous analgesia pump significantly later than SL group did (P<0.05). The total consumptions of sufentanil in PH and SL groups were significantly lower than that of SH group (P<0.05). The incidence rates of bradycardia and postoperative chill in PH and SH groups were significantly higher than those of SL group (P<0.05). Anesthesia by infusion of high-dose remifentanil plus sevoflurane caused postoperative hyperalgesia which was relieved through intravenous anesthesia with propofol.

Measuring sensory and pain thresholds by Semmes-Weinstein monofilaments in patients with leg ulcers: a pilot study

Objective: Pain is a common and disabling symptom in patients with leg ulcers. Clinical quantification of pain mostly depends on subjective pain reports, which do not reveal underlying mechanisms. The aim of this pilot study is to identify mechanisms underlying the pain in patients with leg ulcers by documenting alterations in pain processing using quantitative sensory testing. Methods: In nine ulcer patients the mechanical sensory thresholds and the mechanical pain thresholds were determined by Semmes-Weinstein monofilaments (SWM) at three different sites: on the contralateral (unaffected) leg, on the skin of the affected leg 10cm from the ulcer margin, and on the affected leg, close (1–2cm) to the ulcer margin. Besides the mechanical sensory thresholds and mechanical pain thresholds, pain at the site of the ulcer, using an 11-point numeric rating scale (NRS), was documented. Results: Mechanical sensory thresholds were increased in all subjects. Almost half (44%) of patients consistently showed allodynia at the unaffected site. The lowering of mechanical pain thresholds correlated with higher scores on the NRS. Conclusion: All patients showed diminished touch and/or protective sensation, which might have contributed to ulcer development via (partial) loss of protective function. The allodynia at the unaffected site suggests the presence of central sensitisation of pain processing.