Constriction Injury Of Sciatic Nerve Research Articles

Ontogenic expression profiles and oxaliplatin regulation of leptin expression in mice dorsal root ganglion.

Leptin is widely distributed in many tissues, including the nervous system. However, the ontogeny of leptin expression in the dorsal root ganglion (DRG) is unclear. Recent studies have shown that leptin is involved in the regulation of neuropathic pain induced by nerve injury. Our previous results showed that exogenous leptin administration alleviated the pain behaviors induced by chronic constriction sciatic nerve injury. In the present study, the ontogenic expression of leptin was detected in the DRG of the mouse embryo at days 15.5 (E15.5), E17.5, and E19.5 of gestation and in the postnatal mouse at days 5 (P5), P15, and P25, and in the adult mouse. Leptin immunoreactivity and mRNA were not found in DRG at E15.5. The percentage of leptin immunopositive (leptin) neurons was about 27% at E17.5. It continued to increase to about 70% at P5. From P5 to P15, there was no significant change. The proportion of DRG neurons positive for leptin decreased after P15 and there were about 41% leptin neurons in adults. The expression profile of leptin mRNA is similar to leptin immunoreactivity. Oxaliplatin (OXA) is an effective platinum-based drug used as first-line chemotherapy for advanced colorectal cancer. However, it may induce neuropathic pain. In the current study, we found that the expression of leptin was increased in the lumbar 4-6 DRG of OXA-treated mice. These results indicate that leptin is involved in the regulation of DRG development and OXA-induced neuropathic pain.

Recruitment of dorsal midbrain catecholaminergic pathways in the recovery from nerve injury evoked disabilities.

BackgroundThe periaqueductal gray region (PAG) is one of several brain areas identified to be vulnerable to structural and functional change following peripheral nerve injury. Sciatic nerve constriction injury (CCI) triggers neuropathic pain and three distinct profiles of changes in complex behaviours, which include altered social and sleep–wake behaviours as well as changes in endocrine function. The PAG encompasses subgroups of the A10 dopaminergic and A6 noradrenergic cell groups; the origins of significant ascending projections to hypothalamic and forebrain regions, which regulate sleep, complex behaviours and endocrine function. We used RT-PCR, western blots and immunohistochemistry for tyrosine hydroxylase to determine whether (1) tyrosine hydroxylase increased in the A10/A6 cells and/or; (2) de novo synthesis of tyrosine hydroxylase, in a ‘TH-naïve’ population of ventral PAG neurons characterized rats with distinct patterns of behavioural and endocrine change co-morbid with CCI evoked-pain.ResultsEvidence for increased tyrosine hydroxylase transcription and translation in the constitutive A10/A6 cells was found in the midbrain of rats that showed an initial 2–3 day post-CCI, behavioural and endocrine change, which recovered by days 5–6 post-CCI. Furthermore these rats showed significant increases in the density of TH-IR fibres in the vPAG.ConclusionsOur data provide evidence for: (1) potential increases in dopamine and noradrenaline synthesis in vPAG cells; and (2) increased catecholaminergic drive on vPAG neurons in rats in which transient changes in social behavior are seen following CCI. The data suggests a role for dopaminergic and noradrenergic outputs, and catecholaminergic inputs of the vPAG in the expression of one of the profiles of behavioural and endocrine change triggered by nerve injury.

Increased excitability of medium-sized dorsal root ganglion neurons by prolonged interleukin-1β exposure is K(+) channel dependent and reversible.

Neuropathic pain resulting from peripheral nerve injury is initiated and maintained by persistent ectopic activity in primary afferent neurons. Sciatic nerve injury increases the excitability of medium-sized dorsal root ganglion (DRG) neurons. Levels of the inflammatory cytokine interleukin 1β (IL-1β) increase and peak after 7days. Five to six days of exposure of medium sized DRG neurons to 100pm IL-1β promotes persistent increases in excitability which abate within 3-4days of cytokine removal. This is associated with a profound attenuation of K(+) channel currents but only modest increases in function of cyclic nucleotide-sensitive hyperpolarization-activated channels (HCNs) and of voltage-gated Na(+) and Ca(2+) channel currents. It is unlikely, therefore, that direct interaction of IL-1β with DRG neurons is capable of initiating an enduring phenotypic shift in their electrophysiological properties that follows sciatic nerve injury. The findings also underline the importance of K(+) channel modulation in the actions of inflammatory mediators on peripheral neurons. Chronic constriction injury of rat sciatic nerve promotes signs of neuropathic pain. This is associated with an increase in the level of interleukin 1β (IL-1β) in primary afferents that peaks at 7days. This initial cytokine exposure has been proposed to trigger an enduring alteration in neuronal phenotype that underlies chronic hyper-excitability in sensory nerves, which initiates and maintains chronic neuropathic pain. We have shown previously that 5-6days of exposure of rat dorsal root ganglia (DRGs) to 100pm IL-1β increases the excitability of medium-sized neurons. We have now found using whole-cell recording that this increased excitability reverts to control levels within 3-4days of cytokine removal. The effects of IL-1β were dominated by changes in K(+) currents. Thus, the amplitudes of A-current, delayed rectifier and Ca(2+) -sensitive K(+) currents were reduced by ∼68%, ∼64% and ∼36%, respectively. Effects of IL-1β on other cation currents were modest by comparison. There was thus a slight decrease in availability of high voltage-activated Ca(2+) channel current, a small increase in rates of activation of hyperpolarization-activated cyclic nucleotide-gated channel current (IH ), and a shift in the voltage dependence of activation of tetrodotoxin-sensitive sodium current (TTX-S INa ) to more negative potentials. It is unlikely, therefore, that direct interaction of IL-1β with DRG neurons initiates an enduring phenotypic shift in their electrophysiological properties following sciatic nerve injury. Persistent increases in primary afferent excitability following nerve injury may instead depend on altered K(+) channel function and on the continued presence of slightly elevated levels IL-1β and other cytokines.

The ventral portion of the anterior pretectal nucleus controls descending mechanisms that initiate neuropathic pain in rats.

Stimulating the dorsal anterior pretectal nucleus (dAPtN) in rats is more effective than stimulating the ventral APtN (vAPtN) at reducing tail-flick latency, whereas stimulation of the vAPtN is more effective at reducing postoperative pain behaviour. This study examines whether a cell lesion caused by injecting N-methyl-D-aspartate into the dAPtN or vAPtN changes the withdrawal threshold of a rat hind paw during different phases of the tactile hypersensitivity induced by a chronic constriction injury (CCI) of the contralateral sciatic nerve. The number of Fos immunoreactive cells in the APtN was also evaluated. The rats whose vAPtN was lesioned 2 days before CCI had more intense tactile hypersensitivity 2 days after CCI than that of the control group, but the groups were not different 7 days after the CCI. The rats whose vAPtN was lesioned 5 days after CCI had withdrawal thresholds that did not differ significantly 7 days after the CCI. The tactile hypersensitivity of the rats whose dAPtN was lesioned 2 days before or 5 days after CCI was not different from that of the control on the second and seventh days after the CCI. The number of Fos immunoreactive cells in the vAPtN and dAPtN increased 2 days after CCI, but did not differ from that in the control 7 days after CCI. We conclude that vAPtN and dAPtN cells are activated by nerve injury; the vAPtN exerts inhibitory control of the initial phase of neuropathic pain whereas the dAPtN does not appear to exert an inhibitory effect in neuropathic processing.

Anti-allodynic Efficacy of NMDA Antagonist Peptide and Noradrenaline Alone and in Combination in Rodent Neuropathic Pain Model

BackgroundThe present experiment was conducted to identify the cooperative effect of serine histogranin (SHG) and noradrenaline in alleviating peripheral neuropathic pain.MethodsChronic constriction injury of the right sciatic nerve was used to induce chronic neuropathic pain. For drug delivery, a PE10 tube was inserted into the subarachnoid space. Acetone drops and a 44℃ water bath were used to evaluate the cold and heat allodynia, respectively. Placing and grasping reflexes were used to assess the locomotor system.ResultsSHG at 0.5 and 1 µg significantly (P < 0.05) decreased the thermal allodynia. The cold allodynia was also significantly reduced by intrathecal injections of 0.5 (P < 0.05) and 1 µg (P < 0.001) of SHG. 1 µg of noradrenaline, but not 0.5 µg, significantly alleviated the cold (P < 0.01) and thermal (P < 0.05) allodynia. The ameliorating effect of noradrenaline or SHG disappeared when the two compounds were administrated in equal concentrations. A significant difference (P < 0.01 in the acetone and P < 0.05 in the heat) was observed in the groups under equal doses of the two compounds, with a lower effectiveness of the combination therapy.ConclusionsOur findings suggest that the simultaneous administrations of noradrenaline and SHG do not result in synergistic analgesia, and combination therapy may not be a good approach to the treatment of chronic neuropathic pain syndrome.

H2 Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain.

Neuropathic pain (NP) is characterized by persistent pain, tactile allodynia, or hyperalgesia. Peripheral nerve injury contributes to rapid progress of inflammatory response and simultaneously generates neuropathic pain. Hydrogen (H2) has anti-inflammation, anti-apoptosis, and anti-oxidative stress effects. Therefore, we hypothesized that H2 treatment could alleviate allodynic and hyperalgesic behaviors and the release of inflammatory factors in rats with neuropathic pain. Peripheral neuropathic pain was established by chronic constriction injury of sciatic nerve in rats. H2 was given twice through intraperitoneal injection at a daily dose of 10mL/kg during days 1-7 after the operation. Hyperalgesia and allodynia were tested, pro-inflammatory factors of dorsal root ganglia (DRG) and the spinal cord were measured by enzyme-linked immunosorbent assay (ELISA) during days 1-14 after the operation, and heme oxygenase (HO)-1 messenger RNA (mRNA) and protein expression and activities were measured at day 14 after sciatic nerve injury in rats. After Sn (IV) protoporphyrin IX dihydrochloride (SnPP)-IX, hemin, and carbon monoxide-releasing molecule (CORM)-2 had been given for chronic constriction injury (CCI) in rats, the above indicators were assessed. We found that H2 clearly inhibited hyperalgesia and allodynia in neuropathic pain and also attenuated the pro-inflammatory cytokines TNF-α, IL-1β, and high-mobility group box (HMGB) 1. H2 improved HO-1 mRNA and protein expression and activities in the process of pain. SnPP-IX reversed the inhibitory effect of H2 on hyperalgesia and allodynia and on pro-inflammatory cytokines in DRG and the spinal cord. The antinociceptive and anti-inflammatory effects of H2 were involved in the activation of HO-1/CO signaling during neuropathic pain in rats.

Glial cell line-derived neurotrophic factor-mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic pain.

The locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC. Rats with chronic constriction injury (CCI) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days and changes in mechanical allodynia and thermal hyperalgesia were assessed. The α2 -adrenoceptor antagonist yohimbine was injected intrathecally to assess the involvement of descending inhibition in GDNF-mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF. Both mechanical allodynia and thermal hyperalgesia were attenuated 24 h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF. The analgesic effects of GDNF were partly, but significantly, inhibited by prior injection of U0126 into the LC. GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.

Active immunization with myelin-derived altered peptide ligand reduces mechanical pain hypersensitivity following peripheral nerve injury.

BackgroundT cells have been implicated in neuropathic pain that is caused by peripheral nerve injury. Immunogenic myelin basic protein (MBP) peptides have been shown to initiate mechanical allodynia in a T cell-dependent manner. Antagonistic altered peptide ligands (APLs) are peptides with substitutions in amino acid residues at T cell receptor contact sites and can inhibit T cell function and modulate inflammatory responses. In the present study, we studied the effects of immunization with MBP-derived APL on pain behavior and neuroinflammation in an animal model of peripheral nerve injury.MethodsLewis rats were immunized subcutaneously at the base of the tail with either a weakly encephalitogenic peptide of MBP (cyclo-MBP87-99) or APL (cyclo-(87-99)[A91,A96]MBP87-99) in complete Freund’s adjuvant (CFA) or CFA only (control), following chronic constriction injury (CCI) of the left sciatic nerve. Pain hypersensitivity was tested by measurements of paw withdrawal threshold to mechanical stimuli, regulatory T cells in spleen and lymph nodes were analyzed by flow cytometry, and immune cell infiltration into the nervous system was assessed by immunohistochemistry (days 10 and 30 post-CCI). Cytokines were measured in serum and nervous tissue of nerve-injured rats (day 10 post-CCI).ResultsRats immunized with the APL cyclo-(87-99)[A91,A96]MBP87-99 had significantly reduced mechanical pain hypersensitivity in the ipsilateral hindpaw compared to cyclo-MBP87-99-treated and control rats. This was associated with significantly decreased infiltration of T cells and ED1+ macrophages in the injured nerve of APL-treated animals. The percentage of anti-inflammatory (M2) macrophages was significantly upregulated in the APL-treated rats on day 30 post-CCI. Compared to the control rats, microglial activation in the ipsilateral lumbar spinal cord was significantly increased in the MBP-treated rats, but was not altered in the rats immunized with the MBP-derived APL. In addition, immunization with the APL significantly increased splenic regulatory T cells. Several cytokines were significantly altered after CCI, but no significant difference was observed between the APL-treated and control rats.ConclusionsThese results suggest that immune deviation by active immunization with a non-encephalitogenic MBP-derived APL mediates an analgesic effect in animals with peripheral nerve injury. Thus, T cell immunomodulation warrants further investigation as a possible therapeutic strategy for the treatment of peripheral neuropathic pain.

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice.

The present study was designed to investigate the effect of ramipril (angiotensin-converting enzyme inhibitor) on the chronic constriction injury of sciatic nerve induced neuropathic pain in mice. The neuropathic pain was induced by four loose ligations of the right sciatic nerve in mice. The battery of behavioral tests, i.e. plantar, pin prick, tail flick, tail pinch, rota rod tests, were performed to assess the degree of thermal and mechanical hyperalgesia in ipsilateral paw and tail, and motor in-coordination activity respectively. In addition, the biochemical tests, i.e. total protein, thiobarbituric acid reactive substances and reduced glutathione, were also performed in sciatic nerve tissue samples. The administration of ramipril (2 and 4 mg/kg, p.o.) significantly attenuated chronic constriction injury-induced rise in peripheral as well as central pain sensitivity (thermal and mechanical) along with impairment of motor in-coordination activity. Further, it also produces ameliorative effects on chronic constriction injury-induced rise in thiobarbituric acid reactive substances and decrease in glutathione levels when compared with a normal control group. It may be concluded that angiotensin-converting enzyme inhibitor may be a potential new target for the management of neuropathic pain.

Intrathecal injection of monocarboxylate transporter inhibitor α-cyano-4-hydroxy-cinnamate attenuates neuropathic pain in rats

Objective To investigate the effects of intrathecal injection of α-cyano-4-hydroxy-cinnamate(4-CIN) in rats with neuropathic pain induced by chronic constriction injury of sciatic nerve(CCI). Methods Eighteen male SD rats were divided randomly into 3 groups(n=6): sham group (group S), CCI model group (group C0) and 4-CIN group ( group C1). Group C0 and C1 were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve; and group S were treated as sham operated rats. Two days after operation, group C1 received intrathecal injection of 100 μmol 4-CIN dissolved in 10% DMSO 10 μl, while group C0 received intrathecal injection of 10% DMSO 10 μl only.The paw withdrawal thermal latency(PWTL) and paw withdrawal mechanical threshold(PWMT) were tested 1 d before operation and 1 d, 3 d, 7 d, 10 d, 14 d after operation(T0-5). Results The basic values of PWMT and PWTL before operation showed no statistically significant differences among the three groups.On T1-5, the PWMT((11.71±2.81)g, (9.76±1.00)g, (8.22±1.33)g, (6.50±1.48)g, (4.67±1.03)g) and PWTL((11.36±2.18)s, (11.60±2.54)s, (8.54±1.42)s, (7.59±1.00)s, (6.88±0.42)s) in group C0 were significantly lower than those in group S (P 0.05). Conclusion Intrathecal administration of 4-CIN can attenuate neuropathic pain in rats induced by CCI. Key words: Monocarboxylate transporter; Inhibitor 4-CIN; Neuropathic pain; Spinal cord

P.2.g.004 Vortioxetine modulates GABA and glutamate marker expression in a subchronic PCP model of impaired executive functioning in rats

Chronic constriction injury (CCI) of rat sciatic nerve produces a specific pattern of electrophysiological changes in the superficial dorsal horn that lead to central sensitization that is associated with neuropathic pain. These changes can be recapitulated in spinal cord organotypic cultures by long term (5–6 days) exposure to brain-derived neurotrophic factor (BDNF) (200 ng/ml). Certain lines of evidence suggest that both CCI and BDNF increase excitatory synaptic drive to putative excitatory neurons while reducing that to putative inhibitory interneurons. Because BDNF slows the rate of discharge of synaptically-driven action potentials in inhibitory neurons, it should also decrease the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) throughout the superficial dorsal horn. To test this possibility, we characterized superficial dorsal horn neurons in organotypic cultures according to five electrophysiological phenotypes that included tonic, delay and irregular firing neurons. Five to 6 days of treatment with 200 ng/ml BDNF decreased sIPSC frequency in tonic and irregular neurons as might be expected if BDNF selectively decreases excitatory synaptic drive to inhibitory interneurons. The frequency of sIPSCs in delay neurons was however increased. Further analysis of the action of BDNF on tetrodotoxin-resistant miniature inhibitory postsynaptic currents (mIPSC) showed that the frequency was increased in delay neurons, unchanged in tonic neurons and decreased in irregular neurons. BDNF may thus reduce action potential frequency in those inhibitory interneurons that project to tonic and irregular neurons but not in those that project to delay neurons.

Exercise-Induced Hypoalgesia Profile in Rats Predicts Neuropathic Pain Intensity Induced by Sciatic Nerve Constriction Injury

The aim of this study was to investigate the predictive value of exercise-induced hypoalgesia (EIH) profile on pain intensity induced by nerve injury in a rat model. EIH was tested by evaluating the percentage of withdrawal responses to a train of 30 mechanical stimuli on the hind paw before and after 180 seconds of exercise on a rotating rod. The rats were grouped into low, medium, and high EIH based on their reduction in the percentage of withdrawal responses before and after exercise. Rats from each group then underwent left sciatic nerve constriction injury. Mechanical allodynia, mechanical hyperalgesia, and heat allodynia were assessed in the affected and contralateral hind paws prior to and 3 and 7 days following the procedure. The low EIH rats demonstrated increased hypersensitivity at baseline and developed significantly more severe heat allodynia, mechanical allodynia, and hyperalgesia 3 and 7 days following the injury compared to the medium and high EIH rats. Moreover, the low EIH rats developed contralateral heat allodynia following the injury. The EIH of habituated and nonhabituated rats was compared to study the role of stress on the hypoalgesic effect. No significant differences were found between the habituated and nonhabituated rats at baseline and 1 and 5 minutes after the exercise. PerspectiveEIH profile was found to be predictive of pain severity following nerve injury. It may suggest that selected patients with faulty pain modulation are at risk for developing chronic pain following injury or surgical procedures. EIH may represent a preoperative means to detect this predisposition and enable proactive management.

Expression pattern of connective tissue growth factor in dorsal root ganglia during chronic nerve compression

Objective To investigate the expression of connective tissue growth factor (CTGF) in the nerve cells of dorsal root ganglion (DRG) after chronic sciatic nerve compression.Methods The chronic sciatic nerve constriction injury was made in 40 male SD rats by Mackinnon method.At the 0 week,2nd week,4th week and 6.th week after the operation,L4-L6 DRG that connected to sciatic nerve were harvested.The neurons were separated from the L4-L6 DRG.Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were applied to detect the expression and synthesis of CTGF in the neurons from the DRG.Results The expression and synthesis of CTGF were detected in the nerve cells of normal DRG.After chronic compression of the sciatic nerve,the CTGF expression level was 5.527 3 ± 0.013 6,6.056 7 ± 0.141 5 and 4.533 3 ± 0.092 9,respectively,and CTGF synthesis was 13.96 ± 1.23,17.97 ± 1.35 and 15.63 ±0.87,respectively.At the 2nd week after chronic compression of the sciatic nerve,the expression and synthesis of CTGF were increased dramatically.At the 4th week,the expression and synthesis of CTGF were increased obviously and reached the peak.At the 6th week,the expression and synthesis of CTGF were decreased slowly,but higher than on the normal side.Conclusion CTGF not only participates in the pathophysiological process of the nerve cells of DRG after the chronic compression of sciatic nerve,but also plays an important role in protecting the nerve cells. Key words: Sciatic nerve ; Chronic compression ; Dorsal root ganglion ; Connective tissue growth factor

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats.

The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Differential expression of alpha-adrenoceptor subtypes in rat dorsal root ganglion after chronic constriction injury.

mRNAs of alpha-adrenoceptor (α-AR) subtypes are found in neurons in dorsal root ganglion (DRG) and change after peripheral nerve injury. In this study, the distribution of α-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve (CCI). Using immunofluorescence technique, it was found that α1A-, α1B-, and α2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. α1D- and α2C-AR was also expressed in all size neurons in normal DRG. However, α1D-AR was significantly increased and α2C-AR was decreased in small size neurons 14 days post CCI. α2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of α1A- and α2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of α-AR subtypes in DRG neurons, and the distribution and levels of expression of α-AR subtypes change differently after CCI. The up-regulation of α-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.

Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2weeks in doses of 50, 100 and 200mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

Effects of resveratrol on spatial memory ability in chronic constriction injury of sciatic nerve mice

Objective To investigate spatial memory ability of intraperitoneal injection of resveratrol in a mice model of chronic constriction injury of sciatic nerve(CCI). Methods Forty-four C57BL/6 mice were divided randomly into 4 groups: sham group(n=14), CCI group(n=14), resveratrol pre-treatment group (i.p. resveratrol 100 mg/kg 30 minutes before CCI model, n=8) and resveratrol post-treatment group (i.p. resveratrol 100 mg/kg 14 days after CCI model, n=8). CCI group, resveratrol pre-treatment group and resveratrol post-treatment group were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve. In sham-operated controls, an identical surgical procedure was performed, except that the sciatic nerve was not ligated. This was accomplished by using intellicage for mice by newbehavior to record their spatial memory after surgery. Results (1) Resveratrol pre-treatment group showed improved spatial memory ability compared with sham group and CCI group during day 17-21(17 d: (55.80±7.66)%, (51.20±7.94)%; 18 d: (60.20±3.89)%, (49.80±8.61)%; 19 d: (62.20±7.25)%, (51.20±6.83)%; 20 d: (63.00±9.69)%, (48.40±8.84)%; 21 d: (56.80±7.52)%, (47.20±4.54)%)(P<0.05), compared with CCI group.(2)From day 26, the spatial memory damage was observed in mice with CCI (26 d: (37.50±5.50)%, (51.80±9.01)%; 27 d: (37.25±4.19)%, (51.20±5.76)%; 28 d: (42.25±3.50)%, (52.80±7.52)%)(P<0.05), compared with sham group. And this damage could be reversed by resveratrol, which was injected when the chronic pain was stable(26 d(46.60±5.27)%, 27 d(54.00±7.31)%, 28 d(52.60±4.39)%), compared with CCI group(P<0.05). Conclusion Chronic constriction injury of sciatic nerve mice due to spatial memory impairment can be improved by resveratrol. Key words: Chronic pain; Resveratrol; Spatial memory impairment; Intellicage

Effects of Akt1 gene knockout on pain behaviour induced by chronic constriction injury of sciatic nerve in mice

Objective To investigate the effects of Akt3 gene knockout on neuropathic pain behaviors induced by chronic constriction injury of sciatic nerve (CCI). Methods Experiment was divided into two groups: Akt3 knockout group(Akt3-/-, n=12), wild type group(WT, n=12). Randomly numbered, the right sciatic nerve of mice were received the operation of chronic constriction injury. Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested on day 1 before operation and day 1, 3, 5, 7, 10, 14, 17, 21 after CCI. Results The basic values of PWMT(right: (1.09±0.20)g, (1.17±0.22)g; left: (1.17±0.15)g, (1.22±0.23)g, P>0.05) and PWTL(right: (6.18±1.11)s, (6.20±1.25)s; left: (5.82±0.91)s, (5.92±1.71)s, P>0.05) had no statistically significant differences between two groups.On day 1 after operation, compared with basic values, the PWMT and PWTL of the right paw in both Akt3-/- group and WT group decreased significantly (P 0.05). However, compared to left paw, the PWMT and PWTL of the right paw of the two groups were obviously lower(P<0.05). Conclusion The neuropathic pain induced by CCI increased in Akt3 gene knockout mice. Key words: Akt3; Gene knock out; Neuropathic pain

Evaluation of lyophilized extract of leaves of Tridax procumbens Linn. in rodent models of inflammatory and neuropathic pain

The aim of present study was to evaluate effect of lyophilized extract of Tridax procumbens Linn. in rodent models of inflammatory and neuropathic pain. The antiallodynic and antihyperalgesic activity of Tridax procumbens was assessed in Chronic Constriction Injury of Sciatic Nerve in rats (CCI) and Scald pain model in rats (burning pain) respectively at 100,200 and 400 mg/kg, p.o. In CCI model, the extract shows the dose dependent antiallodynic activity 60 min. post dose. In Scald pain model, extract shows the significant antihyperalgesic activity at 200 and 400 mg/kg at 60 and 90 min. post dose. The lyophilized extract of Tridax procumbens was found to be effective in neuropathic and inflammatory pain, suggesting its possible action via peripheral mechanisms. The activity may be attributed to the presence of flavonoids such as Quercetin.

Commiphora mukul attenuates peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats

ObjectiveThe management of neuropathic pain remains unsatisfactory till date, despite immense advances in the therapeutic strategies. Commiphora mukul (CM), also known as Commiphora wightii, is well known in the traditional Indian system of medicine, and has been used to treat ailments such as obesity, bone fractures, arthritis, inflammation, cardiovascular diseases, and lipid disorders. The present study was performed to investigate the effect of CM on peripheral neuropathic pain in rats.MethodsNeuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, CM was orally administered for 2 weeks in doses of 50, 100, and 200 mg/kg, and pain assessment was performed by employing the behavioral tests for thermal hyperalgesia (hot-plate and tail-flick tests) and cold allodynia (acetone test).ResultsFollowing the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of CM (50 mg/kg) did not have any effect on the hot-plate and tail-flick tests, but significant anti-allodynic effect was observed in the acetone test. Furthermore, administration of CM (100 mg/kg) caused significant decrease in pain as observed on the tail-flick and acetone tests, but not in the hot-plate test. CM in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot-plate and tail-flick latencies, and decreased paw withdrawal duration (in acetone test).DiscussionTherefore, the present study suggests that CM may be used in future as a treatment option for neuropathic pain.