Abstract Here, we established a program of low-intensity aerobic exercise and compared the effects of exercise preoperative, postoperative, and a combination of both pre- and postoperative protocols ...on recovery from sciatic nerve crush injury in mice using behavioral, biochemical, and morphological assays. Sciatic nerve crush was performed in adult male mice. The animals were submitted to preoperative (for 2 weeks), postoperative (for 2 weeks), and a combination of preoperative-postoperative (for 4 weeks) training protocols. During the training period, functional recovery was monitored using the Sciatic Functional Index, the Sciatic Static Index, and mechanical and cold hypersensitivity analyses. Morphological and biochemical alterations were analyzed on the 14th day post-crushing. The functional recovery values of all of the exercised groups were significantly better than the nonexercised group. Biochemically, all of the exercise groups showed a reduction in the increase of interleukin-1β (IL-1β) in the sciatic nerve and in the IL-1β and interleukin-6 receptor (IL-6R) levels in the spinal cord. However, the levels of tumor necrosis factor alpha (TNF-α) decreased only in the postoperative group and in the combination exercise protocols. In the morphological analysis, the combination exercise subjects presented an increase in fiber and axon diameter, in the myelination degree and in the number of myelinated fibers. The present study showed that pre- and postoperative exercise achieved values for functional and morphological sciatic nerve regeneration that were significantly better than either the preoperative or postoperative protocols. This experimental study suggests that physical exercise can restore motor and nerve function to a substantial degree when performed using a prophylactic and therapeutic approach.
Highlights ► Exercise attenuates mechanical allodynia on complex regional pain syndrome type I. ► Caffeine reverses antiallodynic effect produced by high-intensity swimming exercise. ► Antiallodynic ...effect caused by exercise involves the activation of the A1 receptors.
Highlights ► Inhibition of Glycogen Synthase Kinase-3 produces antihyperalgesia. ► Neuropathic pain is reduced by AR-A014418. ► GSK-3 as novel pharmacological target for the treatment of chronic ...pain. ► Serotonergic system is involved in the antihyperalgesic effect of AR-A014418. ► Catecholaminergic system is involved in the antihyperalgesic effect of AR-A014418.
It is known that (−)-linalool is a competitive antagonist of NMDA receptors, which play a key role in the learning and memory processes; however, only a few studies have reported a possible ...interference of (−)-linalool in memory. The purpose of this study was to investigate the (−)-linalool effects on acquisition of short- and long-term memories through the objects recognition task, inhibitory avoidance test and habituation to a novel environment. Furthermore, the open field test was used to investigate the interference of (−)-linalool in motivation, locomotion and exploration by animals. Wistar male adult rats received an intraperitoneal injection (i.p.) of saline (NaCl 0.9%), tween 5% or (−)-linalool (50 or 100mg/kg) before training in the tasks; MK-801 (0.1mg/kg), a glutamate antagonist, was used as positive control. Short-term (STM) and long-term (LTM) memories were tested 1.5 and 24h after training, respectively, in the inhibitory avoidance and recognition objects. The results suggested that (−)-linalool (as 50- and 100-mg/kg doses) impaired LTM acquisition, but not STM acquisition, in the object recognition task. In the inhibitory avoidance test, animals receiving linalool (both doses) showed impairment in acquisition of both memories measured. In the open field test, the animals that received (−)-linalool showed no significant difference in the crossings and latency to start the locomotion in any of the doses tested, although (−)-linalool 100mg/kg reduced rearing behavior. When re-exposed to open field 24h after training, the rats that received (−)-linalool 100mg/kg showed no habituation. Taken together, these data suggested that (−)-linalool was able to impair the acquisition of memory in rats, which can be associated to (−)-linalool antagonist capacity as regards NMDA glutamatergic receptors, since other glutamate antagonists also seem to affect memory.
Complex regional pain syndrome (CRPS) is a disorder that involves abnormal inflammation and nerve dysfunction frequently resistant to a broad range of treatments. Peripheral nerve stimulation with ...electroacupuncture (EA) has been widely used in different clinical conditions to control pain and inflammation; however, the use of EA in the treatment of CRPS is under investigation. In this study, we explore the effects of EA on hyperalgesia and edema induced in an animal model of chronic post-ischemia pain (CPIP model) and the possible involvement of endothelin receptor type B (ET
B
) in this effect. Female Swiss mice were subjected to 3 h hind paw ischemia/reperfusion CPIP model. EA treatment produced time-dependent inhibition of mechanical and cold hyperalgesia, as well as edema in CPIP mice. Peripheral administration (i.pl.) of BQ-788 (10 nmol), an ET
B
antagonist, prevented EA-induced antihyperalgesia while intrathecal administration prolonged EA’s effect. Additionally, peripheral pre-treatment with sarafotoxin (SRTX S6c, 30 pmol, ET
B
agonist) increased EA anti-hyperalgesic effect. Furthermore, the expression of peripheral ET
B
receptors was increased after EA treatments, as measured by western blot. These results may suggest that EA’s analgesic effect is synergic with ET
B
receptor activation in the periphery, as well as central (spinal cord) ET
B
receptor blockade. These data support the use of EA as a nonpharmacological approach for the management of CRPS-I, in an adjuvant manner to ET
B
receptor targeting drugs.
The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of ...gabapentin (GBP) on nerve regeneration. Male Wistar rats (300 g; n=36) underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001), compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05). Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001), in the density of myelinated fibers/mm2 (P<0.05) and in the degeneration fragments (P<0.01). Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.
Background
Neuropathic pain is severely debilitating and resistant to pharmacological approaches; therefore, the study of therapies to complement its treatment is especially relevant. In a case ...report study, light‐emitting diode therapy (LEDT) has shown analgesic activity as well as reduced the expression of pro‐inflammatory cytokines in a rabbit osteoarthritis model and in calcaneal tendinitis in rats. Although LEDT stimulated morphofunctional recovery after nerve injury in rats, its effect against neuropathic pain has not been tested.
Methods
To that purpose, mice under anaesthesia were subjected to the sciatic nerve crush (SNC) model. On the seventh post‐operative day, after determining analgesic dose (energy density in joules), LEDT (950 nm, 80 mW/cm2, 2.5 J/cm2) was irradiated, daily for a period of 15 days, on the skin over the crush site.
Results
Compared with the SNC group, LEDT reduced mechanical hypersensitivity but not cold hypersensitivity which is induced by SNC, decreased spinal cord and sciatic nerve levels of tumour necrosis factor alpha (TNF‐α) but did not alter interleukin (IL)‐1β and IL‐10 levels, and finally, failed to accelerate motor functional recovery and morphological nerve regeneration.
Conclusion
Taken together, these data provide first‐hand evidence of LEDT effectiveness against neuropathic pain induced by SNC, with corresponding decrease of pro‐inflammatory cytokine levels, both in the sciatic nerve and in the spinal cord, although at a small analgesic dose, LEDT failed to accelerate nerve regeneration.
In this study we hypothesized that swimming during sensitization phase could result in a preventive effect in mice with allergic asthma. Swiss mice were divided into 4 groups: Control and Swimming ...(non-sensitized), OVA and OVA+Swimming (sensitized). The allergic inflammation was induced by 2 intraperitoneal injections and 4 aerosol challenges using ovalbumin. Swimming sessions were performed at high intensity over 3 weeks. 48 h after the last challenge mice were euthanized. Swimming decreased OVA-increased total IgE, IL-1, IL-4, IL-5 and IL-6 levels, as well as the number of total cells, lymphocytes and eosinophils in bronchoalveolar lavage fluid, (p<0.05). Simultaneously, swimming also increased IL-10 and glutathione levels in the Swimming and OVA+Swimming groups (p<0.05). The levels of glutathione peroxidase and catalase were increased only in the Swimming group when compared to all groups (p<0.05). 21 days of swimming resulted in an attenuation of pulmonary allergic inflammation followed by an increase of glutathione levels in the OVA group. Swimming only increased the levels of glutathione peroxidase and catalase in non-sensitized mice (p<0.05). These data suggest that the pulmonary anti-inflammatory effects produced by 3 weeks of high-intensity swimming in this model of OVA-induced asthma may be, at least partly, modulated by reduced oxidative stress and increased IL-10 production.
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