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Effective pain control is an underappreciated aspect of managing opioid withdrawal, and its absence presents a significant barrier to successful opioid detoxification. Accordingly, there is an urgent need for effective non-opioid treatments to facilitate opioid detoxification. l-Tetrahydropalmatine (l-THP) possesses powerful analgesic properties and is an active ingredient in botanical formulations used in Vietnam for the treatment of opioid withdrawal syndrome. In this study, rats receiving morphine (15 mg/kg, i.p.) for 5 days per week displayed a progressive increase in pain thresholds during acute 23 h withdrawal as assessed by an automated Von Frey test. A single dose of l-THP (5 or 7.5 mg/kg, p.o.) administered during the 4th and 5th weeks of morphine treatment significantly improves pain tolerance scores. A 7-day course of l-THP treatment in animals experiencing extended withdrawal significantly attenuates hyperalgesia and reduces the number of days to recovery to baseline pain thresholds by 61% when compared to vehicle-treated controls. This indicates that the efficacy of l-THP on pain perception extends beyond its half-life. As a non-opioid treatment for reversing a significant hyperalgesic state during withdrawal, l-THP may be a valuable addition to the currently limited arsenal of opioid detoxification treatments.

Laboratory rats have excellent learning abilities and are often used in cognitive neuroscience research. The majority of rat studies are conducted on males, whereas females are usually overlooked. Here, we examined sex differences in behavior and tactile sensitivity in littermates during adulthood (5.8–7.6 months of age). We used a battery of behavioral tests, including the 2% sucrose preference test (positive motivation), a free-choice paradigm (T-maze, neutral situation), and associative fear-avoidance learning (negative motivation, aversive situation). Tactile perception was examined using the von Frey test (aversive situation). In two aversive situations (von Frey test and avoidance learning), females were examined during the diestrus stage of the estrous cycle, and ultrasonic vocalization was recorded in both sexes. It was found that (1) females, but not males, lost their body weight on the first day of the sucrose preference test, suggesting sex differences in their reaction to environmental novelty or in metabolic homeostasis; (2) the tactile threshold in females was lower than in males, and females less frequently emitted aversive ultrasonic calls; (3) in the avoidance learning task, around 26% of males (but no females) were not able to learn and experienced frizzing. Overall, the performance of associative fear-avoidance in males was worse than in females. In general, females demonstrated higher abilities of associative learning and less persistently emitted aversive ultrasonic calls.

The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is a cerebral division that is putatively implicated in the chronic pain and depression. We investigated the activity of PrL cortex neurons in Wistar rats that underwent chronic constriction injury (CCI) of sciatic nerve and were further subjected to the forced swimming (FS) test and mechanical allodynia (by von Frey test). The effect of blockade of synapses with cobalt chloride (CoCl2), and the treatment of the PrL cortex with cannabidiol (CBD), the CB1 receptor antagonist AM251 and the 5-HT1A receptor antagonist WAY-100635 were also investigated. Our results showed that CoCl2 decreased the time spent immobile during the FS test but did not alter mechanical allodynia. CBD (at 15, 30 and 60 nmol) in the PrL cortex also decreased the frequency and duration of immobility; however, only the dose of 30 nmol of CBD attenuated mechanical allodynia in rats with chronic NP. AM251 and WAY-100635 in the PrL cortex attenuated the antidepressive and analgesic effect caused by CBD but did not alter the immobility and the mechanical allodynia when administered alone. These data show that the PrL cortex is part of the neural substrate underlying the comorbidity between NP and depression. Also, the previous blockade of CB1 cannabinoid receptors and 5-HT1A serotonergic receptors in the PrL cortex attenuated the antidepressive and analgesics effect of the CBD. They also suggest that CBD could be a potential medicine for the treatment of depressive and pain symptoms in patients with chronic NP/depression comorbidity.

BackgroundThe aerial parts ofBaccharis trimera(Less.) are frequently used as a tea to treat several diseases. Therefore, the aim of this study was to identify the constituents of an aqueous extract ofB. trimera, focusing on their antioxidant, anti-inflammation, and antinociception activities and properties. For that, the researchers performed in vivo assays using the formalin test and Freund’s Complete Adjuvant (FCA) to measure the acute and chronic inflammatory pain in mice. Moreover, the myeloperoxidase enzyme (MPO) was analyzed in the subcutaneous tissue after the FCA injection, together with the counting of lymphocytes in the peripheral blood of the mice.ResultsThe qualitative phytochemical analysis indicated the presence of flavonoids and saponins in theB. trimeraaqueous extract. The high-performance liquid chromatography (HPLC) analyses showed the presence of phenolic compounds, such as chlorogenic acid, ellagic acid, rosmarinic acid, as well as flavonoids, such as rutin, quercetin, and luteolin. The DPPH assay was used in order to measure the antioxidant activity of the aqueous extract ofB. trimeraand this showed an IC50of 118.18 ± 1.02 μg/mg. The data from the formalin test demonstrated that a single dose of the aqueous extract ofB. trimerawas not able to decrease the nociceptive behavior during the neurogenic phase, at any of the tested doses (20, 40, or 80 mg/kg p.o.). However, during the inflammatory phase of this test, the aqueous extract ofB. trimeraat 80 mg/kg (p.o.) significantly decreased the nociceptive behavior, showing more effectiveness when compared to the other tested doses (p B. trimera(80 mg/kg p.o.) significantly reduced mechanical allodynia (p p p B. trimera(80 mg.kg− 1p.o.) and diclofenac sodium.ConclusionTaken together, the present data reinforces the potential of theB. trimeraaqueous extract as an anti-inflammatory and analgesic compound.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2021-11-05T20:17:17Z No. of bitstreams: 1 Carla Bernardo Soldera.pdf: 2530684 bytes, checksum: 44fa94c5fefa5b1c49cdb29fa6424f61 (MD5) Made available in DSpace on 2021-11-05T20:17:17Z (GMT). No. of bitstreams: 1 Carla Bernardo Soldera.pdf: 2530684 bytes, checksum: 44fa94c5fefa5b1c49cdb29fa6424f61 (MD5) Previous issue date: 2020-12-17 Contextualization: Traumatic injuries of the peripheral nervous system are common today, being an important medical problem. The aim of the present study was to evaluate the effects of immediate exercise associated with photobiomodulation therapy using LED as a rehabilitation after peripheral nerve injury by crushing the sciatic nerve in Wistar rats. Methodology: 45 Wistar rats were used, randomly divided into 5 groups: Control; Injury; Injury+LEDn+Exercise; Injury+LEDnm+Exercise; Injury+Exercise. The animals were euthanized 7 and 14 days after the operation. Photobiomodulation therapy consisted of the use of 850nm LED, 1cm2 beam area (nerve region total of 4 points, energy per point 0.8J, time per point of 20sec, total energy 3.2J and muscle region total of 8 points, energy per point 0.4J, time per point 10sec, total energy 3.2J), in a punctual way in contact with the animal's skin, with daily applications for 5 consecutive days, starting 2h after the crush injury. For exercise training, a treadmill adapted for training with rats containing lanes and digital speed control was used. The exercise protocol consisted of daily training started 24 hours after the operation, being performed 30 minutes/day, five days a week, without inclination. After each experimental period, functional analysis of gait was performed using the functional sciatic index, analysis of mechanical hyperalgesia using the Von Frey test, analysis of muscle mass to assess muscle atrophy, qualitative and quantitative assessment of muscle morphological aspects and qualitative analysis and quantitative of collagen fibers. Results: Regarding gait assessment, all injured groups showed a worsening in the functional index assessed after 7 and 14 days of injury, and it was observed in 7 days that the Injury+LEDn+Exercise group performed better when compared to the others. injured and treated groups. In 14 days, the Injury+LEDn+Exercise group performed better when compared to the Injury group. Regarding the analysis of muscle mass, after 7 days, all injured groups, treated or not, showed a decrease in the muscle mass ratio indicating an increase in atrophy when compared to the Control group, and the same occurred in 14 days. The Injury+LEDn+Exercise group in 14 days showed an improvement when compared to the Lesion group indicating less muscle atrophy. Regarding hyperalgesia, in the period of 7 and 14 days all injured groups, treated or not, showed a decrease in nociception in relation to the Control group. In 14 days, the Injury+LEDn+Exercise and Injury+LEDnm+Exercise groups showed better results when compared to the Injury group. It was also shown that in the same period that the injured and treated groups with LED both in the nerve region and in the nerve and muscle associated with exercise showed better results when compared to the Injury+Exercise group only. Conclusion: Based on the results, it was possible to conclude that the use of photobiomodulation when applied to the nervous region associated with early-onset exercise can contribute to a functional improvement in gait, reduces muscle atrophy and acts positively on nociception. Contextualização: Lesões traumáticas do sistema nervoso periférico são comuns atualmente, sendo um importante problema médico. O objetivo do presente estudo foi avaliar os efeitos do exercício imediato associado a terapia de fotobiomodulação utilizando LED como reabilitação após lesão nervosa periférica por esmagamento do nervo ciático em ratos Wistar. Metodologia: Foram utilizados 45 ratos da linhagem Wistar, divididos aleatoriamente em 5 grupos: Controle; Lesão; Lesão+LEDn+Exercício; Lesão+LEDnm+Exercício; Lesão+Exercício. Os animais foram eutanasiados em 7, 14 dias de pós-operatório. A terapia de fotobiomodulação consistiu no uso de LED 850 nm, área do feixe de 1cm2 (região nervosa total de 4 pontos, energia por ponto 0,8J, tempo por ponto de 20seg, energia total 3.2J e região muscular total de 8 pontos, energia por ponto 0,4J, tempo por ponto de 10seg, energia total 3.2J), de forma pontual em contato com a pele do animal, com aplicações diárias por 5 dias consecutivos, iniciando 2h após a lesão por esmagamento. Para o treino de exercício, foi utilizada esteira ergométrica adaptada para o treino com ratos contendo raias e controle digital de velocidade. O protocolo de exercício consistiu em treinos diários iniciados após 24horas de pós- operatório sendo realizado 30min/dia, cinco dias por semana, sem inclinação. Após cada período experimental foi realizado a análise funcional da marcha através do índice funcional do ciático, análise da hiperalgesia mecânica através do teste de Von Frey, análise da massa muscular para avaliar a atrofia muscular, avaliação qualitativa e quantitativa dos aspectos morfológicos musculares e análise qualitativa e quantitativa das fibras colágenas. Resultados: Em relação a avaliação da marcha, todos os grupos lesionados apresentaram uma piora no índice funcional avaliado após 7 e 14 dias de lesão, sendo observado em 7 dia que o grupo Lesão+LEDn+Exercício apresentou um melhor desempenho quando comparado com os demais grupos lesionados e tratados. Já em 14 dias o grupo Lesão+LEDn+Exercício apresentou um melhor desempenho quando comparado ao grupo Lesão. No que se diz respeito a análise da massa muscular, após 7 dias, todos os grupos lesionados, tratados ou não demonstraram uma diminuição da relação de massa muscular indicando aumento de atrofia quando comparado ao grupo Controle, sendo que o mesmo ocorreu em 14 dias. O grupo Lesão+LEDn+Exercício em 14 dias demonstrou uma melhora quando comparado ao grupo Lesão indicando uma menor atrofia muscular. Em relação a hiperalgesia, no período de 7 e 14 dias todos os grupos lesionados, tratados ou não demonstraram uma diminuição na nocicepção em relação ao grupo Controle. Já em 14 dias, os grupos Lesão+LEDn+Exercício e Lesão+LEDnm+Exercício apresentaram melhores resultados quando comparados ao grupo Lesão. Foi demonstrado também que no mesmo período que os grupos lesionados e tratados com LED tanto na região nervosa como nervo e músculo associado ao exercício apresentaram melhores resultados quando comparados ao grupo Lesão+Exercício apenas. Conclusão: Com base nos resultados, é possível concluir que o uso da fotobiomodulação quando aplicada na região nervosa associada ao exercício de início precoce pode contribuir para uma melhora funcional da marcha, reduz a atrofia muscular e atua positivamente na nocicepção.

RATIONALE: Over the last decade, oxycodone has become one of the most widely abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem that has prompted a need to develop animal models of OUD that have both face and predictive validity. Oxycodone use in humans is more prevalent in women and leads to pronounced hyperalgesia and irritability during withdrawal. However, unclear is whether current animal models of oxycodone self-administration recapitulate these characteristics in humans. OBJECTIVES: We assessed the face validity of a model of extended-access oxycodone self-administration in rats by examining the escalation of oxycodone intake and behavioral symptoms of withdrawal, including irritability-like behavior and mechanical nociception, in male and female Wistar rats. RESULTS: Both male and female rats escalated their oxycodone intake over fourteen 12-h self-administration sessions. After escalation, female rats administered more drug than male rats. No differences in plasma oxycodone levels were identified, but males had a significantly higher level of oxycodone in the brain at 30 min. Extended access to oxycodone significantly decreased aggressive-like behavior and increased defensive-like behaviors when tested immediately after a 12-h self-administration session, followed by a rebound increase in aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception thresholds during withdrawal indicated pronounced hyperalgesia. No sex differences in irritability-like behavior or pain sensitivity were observed. CONCLUSIONS: The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P

The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer, however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects of an aqueous extract of Forsythia viridissima fruits (EFVF) and its major constituents. Chemical constituents from EFVF were characterized and quantified with the UHPLC-diode array detector method, and three major constituents were identified as arctiin, matairesinol, and arctigenin. The in vitro cytotoxicity was measured by the Ez-cytox viability assay, and the in vivo neuroprotection activity was evaluated by a von Frey test in two rodent animal models that were administered LOHP. EFVF significantly alleviated the LOHP-induced mechanical hypersensitivity in the induction model. EFVF also prevented the induction of mechanical hyperalgesia by LOHP in the pre- and co-treatment of LOHP and EFVF. Consistently, EFVF exerted protective effects against LOHP-induced neurotoxicity as well as inhibited neurite outgrowths in PC12 and dorsal root ganglion cells. Among the major components of EFVF, arctigenin and matairesinol exerted protective effects against LOHP-induced neurotoxicity. Therefore, EFVF may be useful for relieving or preventing LOHP-induced peripheral neuropathy in cancer patients undergoing chemotherapy with LOHP.

The dried fruits of Forsythia viridissima have been prescribed to relive fever, pain, vomiting, and nausea in traditional medicine. Oxaliplatin (LOHP) is used to treat advanced colorectal cancer; however, it frequently induces peripheral neuropathies. This study was done to evaluate the neuroprotective effects of an aqueous extract of Forsythia viridissima fruits (EFVF) and its major constituents. Chemical constituents from EFVF were characterized and quantified with the UHPLC-diode array detector method, and three major constituents were identified as arctiin, matairesinol, and arctigenin. The in vitro cytotoxicity was measured by the Ez-cytox viability assay, and the in vivo neuroprotection activity was evaluated by a von Frey test in two rodent animal models that were administered LOHP. EFVF significantly alleviated the LOHP-induced mechanical hypersensitivity in the induction model. EFVF also prevented the induction of mechanical hyperalgesia by LOHP in the pre- and co-treatment of LOHP and EFVF. Consistently, EFVF exerted protective effects against LOHP-induced neurotoxicity as well as inhibited neurite outgrowths in PC12 and dorsal root ganglion cells. Among the major components of EFVF, arctigenin and matairesinol exerted protective effects against LOHP-induced neurotoxicity. Therefore, EFVF may be useful for relieving or preventing LOHP-induced peripheral neuropathy in cancer patients undergoing chemotherapy with LOHP.

Nerve injury provokes microglial activation, contributing to the sensory and emotional disorders associated with neuropathic pain that do not completely resolve with treatment. In C57BL/6J mice with neuropathic pain induced by chronic constriction of the sciatic nerve (CCI), we evaluated the effects of oltipraz, an antioxidant and anticancer compound, on (1) allodynia and hyperalgesia, (2) microglial activation and pain signaling pathways, (3) oxidative stress, and (4) depressive-like behaviors. Twenty-eight days after surgery, we assessed the effects of oltipraz on the expression of CD11b/c (a microglial marker), phosphoinositide 3-kinase (PI3K)/ phosphorylated protein kinase B (p-Akt), nuclear factor-?B (NF-?B) transcription factor, and mitogen activated protein kinases (MAPK) in the spinal cord, hippocampus, and prefrontal cortex. Our results show that oltipraz alleviates neuropathic pain by inhibiting microglial activation and PI3K/p-Akt, phosphorylated inhibitor of ?Ba (p-I?Ba), and MAPK overexpression, and by normalizing and/or enhancing the expression of antioxidant proteins, nuclear factor erythroid derived-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) in the spinal cord. The inhibition of microglial activation and induction of the Nrf2/HO-1/NQO1 signaling pathway in the hippocampus and/or prefrontal cortex may explain the antidepressant effects of oltipraz during neuropathic pain. These data demonstrate the analgesic and antidepressant effects of oltipraz and reveal its protective and antioxidant properties during chronic pain. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Context: Andrographolide (Andro), found in large quantities in Andrographis paniculata Nees (Acanthaceae), is anti-inflammatory, especially in the central nervous system (CNS) glia. Objective: The objective of this study is to test Andro’s ability to reduce allodynia in a spared nerve injury model. Material and methods: Male 30 g BalbC mice were divided into four groups: (1) Sham-operated control (Sham-group); (2) nerve injured and treated with saline (Saline-group); (3) nerve injured and treated with Andro (Andro-group); (4) nerve injured and treated with non-steroidal anti-inflammatory drugs (NSAIDS) (NSAIDS-group). Andro or NSAIDS (diclofenac salt) were injected intraperitoneally at 5 mg/kg body weight daily. Mechanical allodynia was assessed by von Frey tests at 3, 7, and 14 d. For immunohistochemical analysis, samples were collected at 7 d. Results: The threshold for inducing allodynia increased and the response percentage reduced in the Andro-group when compared with the Saline-group, as well as when compared with NSAIDS groups throughout 3–14 d. The ratio of threshold for OP-Andro/OP-saline and for OP-Andro/OP-NSAIDS groups was 20.42 and 11.67 at 14 d, respectively. The ratio of response percentage for OP-Andro/OP-saline and for OP-Andro/OP-NSAIDS was 0.32 and 0.39 at 14 d, respectively. Interleukin-1 (IL-1) immunostaining in the spinal cord was reduced in the Andro-group. Astrocytic activities were not significantly reduced in the Andro-group compared with the Saline-group at 7 d post-operation (PO) Conclusions: Andro reduced mechanical allodynia more than NSAIDS at the same concentration, and the observed behaviour was associated with a reduction in inflammatory cytokine produced in the spinal cord.

Submitted by DSpace Unilasalle (dspace@unilasalle.edu.br) on 2021-08-03T14:45:27Z No. of bitstreams: 1 asouza.etal.pdf: 1041409 bytes, checksum: 7c3564560a848231e34c4d8068854532 (MD5) Made available in DSpace on 2021-08-03T14:45:27Z (GMT). No. of bitstreams: 1 asouza.etal.pdf: 1041409 bytes, checksum: 7c3564560a848231e34c4d8068854532 (MD5) Previous issue date: 2018 Background: Neuropathic pain is relatively common and occurs in approximately 6–8% of the population. It is associated with allodynia and hyperalgesia. Thus, non-pharmacological treatments, such as transcranial direct current stimulation (tDCS) may be useful for relieving pain. Objectives: This study aimed to investigate the antiallodynic effect of tDCS in a mice model of neuropathic pain, and the underlying neurotransmission systems that could drive these effects. Methods: Male, Swiss mice, weighing 25–35 g, were subjected to partial sciatic nerve ligation (PSNL). Allodynia was assessed using a Von Frey filament (0.6 g). First, the behavioral time-course of these mice was assessed after 5, 10, 15 and 20 min of tDCS (0.5 mA). Second, the mice that underwent PSNL were assigned to either the tDCS (0.5 mA, 15 min) or tDCS sham group, and further assigned to receive either saline or a drug (i.e., naloxone, yohimbine, a-methyl-p-tyrosine, q-chlorophenylalanine methyl ester, caffeine, 1,3-dipropyl-8-cyclopentylxanthine, AM281, AM630, flumazenil, MK-801, or lidocaine). Results: The antiallodynic effect of tDCS lasted 2 h and 4 h, after 10 min and 15 or 20 min of treatment, respectively (P < .001, P < .01, and P < .05, respectively). The antiallodynic effect of tDCS was associated with all the systems that were analyzed, i.e., the opioidergic (P < .01), adenosinergic (P < .001), serotonergic (P < .01), noradrenergic (P < .001), cannabinoid (P < .001), GABAergic, and glutamatergic (P < .001) systems. Lidocaine did not reverse the antiallodynic effect of tDCS (P > .05). Conclusion: The antiallodynic effect of tDCS was associated with different neurotransmitters systems; the duration of these after-effects depended on the time exposure to tDCS.

Approximately 50–70% of patients experience incision-induced mechanical nociception after surgery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether interleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical nociception remains uncertain. In this study, forty rats were divided randomly into the incision surgery (n = 32) and sham surgery (n = 8) groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group received anesthesia, but not an incision. Von Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord (L3–5) showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons (diameter < 20 μm and 20–40 μm) and satellite cells in the dorsal root ganglia of the spinal cord (L3–5) in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons (diameter > 40 μm) at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by incision surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to mechanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by incision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.

The authors examined effects of the joint position before the ischaemia on alternation of the joint angle of a phantom limb. We further investigated which nerve fiber contributes to the alternation. While we first blocked participants’upper arm with cuff?inflation, we assessed changes in the perceived joint angles as well as in sensory test. In the second block of their upper arm, we further assessed changes in the perceived joint angles when the position of the hand was changed immediately before the inflation. These experiments showed that whereas the proximal and distal interphalangeal, metacarpophalangeal and wrist joints of the phantom limb steeply changed from extended position to flexed position at the start of extended position from 10 to 25 min after the start of the inflation, the four joints changed to the opposite direction at the start of flexed position. These findings revealed that perceived joint angles of a phantom hand were changed by the position of the hand immediately before the inflation. On the other hand, while threshold of von Frey test in the thumb was changed until mean 16 min after the start of the inflation, the touch sensation in the thumb was abolished until mean 19 min. From the results of two experiments, acute perceptual distortions of joint angle thus corresponded with paralysis of the large myelinated diameter nerve

The influence of the environment on clinical post-operative pain received recently more attention in human. A very common paradigm in experimental pain research to model the effect of housing conditions is the enriched environment (EE). During EE-housing, rats are housed in a large cage (i.e. social stimulation), usually containing additional tools like running wheels (i.e. physical stimulation). Interestingly, only postsurgical housing effect on post-operative pain was developed during clinical and experimental studies while little is known on the influence of preoperative housing. In this study, our aim was to investigate the influence of housing conditions prior to an operation on the development of post-operative pain, using a rat model of carrageenan-induced inflammatory pain. Four housing conditions were used: a 3-week pre-housing in standard conditions (S-) followed by a post-housing in an EE; a 3-week pre-housing in EE followed by a post-operation S-housing; a pre- and post-housing in EE; a pre- and post-S-housing. The development of mechanical allodynia was assessed by the means of the von Frey test, preoperatively and at day post-operative (DPO) 1, 3, 7, 10, 14, 17, 21, 24 and 28. Our results show that a 3-week preoperative exposure to EE leads to a significant reduction in the duration of the carrageenan-induced mechanical allodynia, comparable with a post-operative exposure to EE. Strikingly, when rats were housed in EE prior to as well as after the carrageenan injection into the knee, mechanical allodynia lasted only 2 weeks, as compared to 4 weeks in S-housed rats.

Testiranje nocicepcije u miševa zahtijevno je područje bihevioralne neuroznanosti koje obuhvaća niz testova kojima se može mjeriti reakcija na tonične i fazične boli. Testove za ispitivanje nocicepcije možemo podijeliti prema obliku podražaja na mehaničke, kemijske, termalne i električne, a prema vremenu njihova trajanja na kratkotrajne (za ispitivanje fazične boli) i dugotrajne (za ispitivanje toničke boli). Prikazan je protokol testova u kojima složeni hiperalgezijski odgovor (kompleksni odgovor životinje na bolni podražaj uz trešnju i lizanje šape i/ili timarenje) najbolje razlikuje miševe s izraženijom nocicepcijom / algezijom.

Using behavioral, immunohistochemical and pharmacological studies, we report here that large thoracic burn injuries remotely induce hindpaw hyperalgesia during the healing stage. During 2-3 weeks after thoracic burn injury when the skin was regenerating from the wound, we observed by formalin test that the number of flinching behaviors significantly increased and simultaneously we observed by von Frey test that rats developed mechano-hyper-algesia in the foot. In the dorsal horn of the lumber spinal cord in burn injured rats, c-Fos expression was significantly augmented after plantar formalin injection. The expression of μ-opioid receptor in burn injured rats was significantly decreased compared with that in sham operated rats. The expression of substance P and CGRP in the lumbar dorsal horn was not different between burn and sham operated animals. We also observed that intrathecal administration of glutamate receptor antagonists(MK801 and CNQX)but not cyclooxigenase-2 an-tagonist(NS-398)reversed the threshold of von Frey test on the foot up to the control level at 2 weeks after injury. Collectively, we analyzed a new pain model showing foot hyperalgesia after thoracic burn injury and demonstrated that neurotransmission of glutamate was enhanced at the lumbar spinal cord level by immunocytochemistry and intrathecal administration of NMDA and non NMDA antagonists. Although the precise mechanism of how remote hyperalgesia at the healing stage developed in this model remains to be confirmed, substances such as trophic factors released from the regenerating skin may cause systemic hyperalgesia including in the foot.

Çalışmamızda ratlarda oluşturulan nöropatik ağrı modelinde gabapentin ve nitrik oksitin etkilerini araştırmayı amaçladık. Yöntem ve Gereç: Çalışma, Adnan Menderes Üniversitesi Tıp Fakültesi Deney Hayvanları Etik Kurulu onayı alındıktan sonra, Tıp Fakültesi Fizyoloji Deneysel Araştırma laboratuarında gerçekleştirildi. Ağırlıkları 250-350 gr arasında değişen Wistar cinsi 63 erkek rat randomize olarak dokuz eşit gruba (n=7) ayrıldı. Tüm gruplardaki ratların başlangıçta ve deneyin sonunda kiloları ölçüldü. Kontrol grubu dışında tüm gruplardaki ratlarda Bennett ve Xie tarafından tarif edilen siyatik sinir ligasyonu ile CCI (Kronik Sıkıştırma Hasarı) modelinin modifiye şekli uygulanarak nöropatik ağrı oluşturuldu. Grup 0 kontrol grubu olarak alındı. Grup SF'e serum fizyolojik, Grup G30'a gabapentin 30 mg/kg, Grup G30+NO'ya gabapentin 30mg/kg +nitrogliserin 1mg/kg, Grup G100'e gabapentin 100 mg/kg, Grup G100+NO'ya gabapentin 100 mg/kg +nitrogliserin 1mg/kg, Grup G300'e gabapentin 300mg/kg, Grup G300+NO'ya gabapentin 300mg/kg +nitrogliserin1mg/kg, Grup NO'ya ise nitrogliserin 1 mg/kg periton içine 21 gün süreyle verildi. Ratların her 10 gramı için 0.07 mL ilaç uygulandı. Deney süresince ratların hareketleri izlendi. Beşinci, onuncu, onbeşinci ve yirmibirinci günlerde von Frey testi yapıldı. Yirmibirinci günde hot-plate testi yapıldı. Bulgular: Beşinci ve onuncu günlerdeki Von Frey ölçümlerinde en yüksek değerlere G30+NO grubunda çıkıldığı gözlendi. Gabapentinin daha yüksek dozlarda verildiği gruplarda von Frey ölçümlerinde elde edilen değerler düşüktü. Hot-plate testinde ise en uzun süre G30 grubunda elde edildi. Sonuç: Ratlarda oluşturduğumuz deneysel nöropatik ağrı modelinde gabapentin intraperitoneal 30 mg/kg+NO 1mg/kg dozunun nöropatik ağrıda mekanik hiperaljezi tedavisinde en etkili olduğu saptandı. Ayrıca gabapentinin 30 mg/kg dozunun termal hiperaljezide en etkili olduğu tespit edildi. To search the effects of gabapentin and nitric oxide on the neuropathic pain model which is made in rats. Material and method: The ethical committe permisssion was obtained from The Genuine Animals Ethic Committee. Wistar type 63 male rats, each of which weighed between 250-350 gr. are divided in to nine equal groups (n=7). Neuropathic pain was constituted at the rats except the control group, by syatic nerve ligation as modified form of CCI (Chronic Constriction Injury) model. Group 0 was the control group. Physiological serum was administered to Group SF. Gabapentin was administered; 30 mg/kg, 100 mg/k, 300 mg/kg to groups G30, G100, G300 respectively. Nitroglycerine was added 1 mg/kg to groups G30+NO, G100+NO, G300+NO respectively. One mg/kg nitroglycerine was administered to Group NO. Drugs were administered intraperitoneally for 21 days. At the fifth, tenth, fifteenth and twentyfirst days; the von Frey test was done. At the twentyfirst day of the study the hot-plate test was done. Findings: The highest values were obtained at the G30+NO group after the von Frey test at the fifth and tenth days. At the groups in which the gabapentin was administered at higher doses the values of the von Frey test were lower. The longest time was obtained at G30 at hot-plate test. Result: At the experimental neuropathic pain model; we found that, administration of 30 mg/kg gabapentin+1 mg/kg nitroglycerin intraperitonealy is the most effective at the treatment of mechanical hiperalgesia. Also it was found that 30 mg/kg gabapentin is the most effective at thermal hiperalgesia.