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Abstract Pain is one of the cardinal signs of inflammation and is present in many inflammatory conditions. Therefore, anti-inflammatory drugs such as NSAIDs also have analgesic properties. We previously showed that prostaglandin D 2 -glycerol ester (PGD 2 -G), endogenously produced by cyclooxygenase-2 from the endocannabinoid 2-arachidonoylglycerol, has anti-inflammatory effects in vitro and in vivo that are partly mediated by DP1 receptor activation. In this work, we investigated its effect in a model of carrageenan-induced inflammatory pain. PGD 2 -G decreased hyperalgesia and edema, leading to a faster recovery. Moreover, PGD 2 -G decreased carrageenan-induced inflammatory markers in the paw as well as inflammatory cell recruitment. The effects of PGD 2 -G were independent from metabolite formation (PGD 2 and 15d-PGJ 2 -G) or DP1 receptor activation in this model. Indeed PGD 2 delayed recovery from hyperalgesia while 15d-PGJ 2 -G worsened the edema. However, while PGD 2 -G decreased hyperalgesia in this model of inflammatory pain, it had no effect when tested in the capsaicin-induced pain model. While the targets mediating the effects of this bioactive lipid in inflammatory pain remain to be elucidated, our findings further support the interest of anti-inflammatory lipid mediators in the management of inflammatory pain. Highlights • PGD 2 -G decreases inflammation and pain in carrageenan-induced hyperalgesia in mice. • These effects are not due to hydrolysis of PGD 2 -G into PGD 2. • 15d-PGJ 2 -G, a PGD 2 -G metabolite, does not mediate its effects on inflammatory pain. • PGD 2 -G decreases macrophage activation and neutrophil infiltration in the paw. • The targets mediating the effects of PGD 2 -G remain to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract Gulf war illness (GWI) is a chronic multi-symptom disease that afflicts 25–33% of troops that were deployed in the 1990–1991 Gulf War. GWI symptoms include cognitive, behavioral and emotional deficits, as well as migraines and pain. It is possible that exposure to Gulf War agents and prophylactics contributed to the reported symptomology. Pyridostigmine bromide (PB) and permethrin (PER) were given to protect from nerve gas attacks and insect vector born disease, respectively. Previous studies have demonstrated that 10 days of exposure to these chemicals can cause symptoms analogous to those observed in GWI, including impairment of long-term memory in mice. Other studies using this model have shown chronic neuroinflammation, and chronic neuroinflammation can lead to altered nociceptive sensitivity. At 10-weeks after the 10-day PB and PER exposure paradigm, we observed lowered nociceptive threshold on the Von Frey test that was no longer evident at 28 weeks and 38 weeks post-exposure. We further determined that vagus nerve stimulation, initiated at 38 weeks after exposure, restores the lowered nociceptive sensitivity. Therefore, stimulating the vagus nerve appears to influence nociception. Future studies are need to elucidate possible mechanisms of this effect. [ABSTRACT FROM AUTHOR]

Highlights • Sumatriptan increased mechanical thresholds in the periorbital region for four days. • Pulsed FUS increased mechanical thresholds post therapy in the periorbital region. • Ablative HIFU did not increase mechanical thresholds post therapy. • FUS may provide a therapeutic option for patients suffering from chronic migraines. Abstract Chronic migraines (CM) are the third most common disease and are refractory to medical treatment in 15% of patients. Currently, temporary relief is achieved with steroid blocks or pulsed radiofrequency ablation, which have short-term benefits. Our project aims to develop a non-invasive treatment for medically refractory chronic migraine, which does not require a permanent implant. This project investigates the safety and effectiveness of pulsed focused ultrasound (FUS) in a validated rodent headache model of cutaneous allodynia associated with chronic migraine (CM) as compared to sumatriptan and ablative lesioning. We demonstrate a significant reduction in mechanical thresholds as measured through Von Frey filaments in CM in the forepaw and periorbital region (p < 0.001). Sumatriptan and pulsed FUS both significantly improve thresholds at day 3 after treatment in the periorbital region. Ablative lesioning has no effect. This study provides initial evidence that FUS may provide an important therapeutic option for patients suffering from CM. [ABSTRACT FROM AUTHOR]

Anxiety disorders are the most prevalent psychiatric disorders, and they are highly comorbid with chronic pain conditions. The central nucleus of the amygdala (CeA) is known not only for its role in the regulation of anxiety but also as an important site for the negative affective dimension of pain. Pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide whose terminals are abundant in the CeA, is strongly implicated in the stress response as well as in pain processing. Here, using Cre-dependent viral vectors, we explored in greater detail the role of the PACAP projection to the CeA that originates in the lateral parabrachial nucleus (LPB). We first performed a circuit mapping experiment by injecting an anterograde Cre-dependent virus expressing a fluorescent reporter in the LPB of PACAP-Cre mice and observing their projections. Then, we used a chemogenetic approach (a Cre-dependent Designer Receptors Activated by Designer Drugs, DREADDs) to assess the effects of the direct stimulation of the PACAP LPB to CeA projection on general locomotor activity, anxiety-like behavior (using a defensive withdrawal test), and mechanical pain sensitivity (using the von Frey test). We found that the CeA, together with other areas, is one of the major downstream projection targets of PACAP neurons originating in the lateral parabrachial nucleus (LPB). In the DREADD experiment, we then found that the selective activation of this neuronal pathway is sufficient to increase both anxiety-like behavior and mechanical pain sensitivity in mice, without affecting general locomotor activity. In conclusion, our data suggest that the dysregulation of this circuit may contribute to a variety of anxiety disorders and chronic pain states, and that PACAP may represent an important therapeutic target for the treatment of these conditions. • We used a circuit mapping approach to assess downstream targets of LPB PACAP neurons. • Considerable PACAP terminals originating in LPB were observed in CeA, BNST, and VMH. • We used chemogenetics to assess the effect of the activation of LPB-CeA PACAP neurons. • Pathway activation increased anxiety-like behavior and mechanical pain sensitivity. • Dysregulation of this circuit may contribute to anxiety disorders and chronic pain. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a debilitating, chronic condition with a significant unmet need for effective treatment options. Recent studies have demonstrated that in addition to neurons, non-neuronal cells such as microglia contribute to the initiation and maintenance of allodynia in rodent models of neuropathic pain. The Ca 2+ - activated K + channel, K Ca 3.1 is critical for the activation of immune cells, including the CNS-resident microglia. In order to evaluate the role of K Ca 3.1 in the maintenance of mechanical allodynia following peripheral nerve injury, we used senicapoc, a stable and highly potent K Ca 3.1 inhibitor. In primary cultured microglia, senicapoc inhibited microglial nitric oxide and IL-1β release. In vivo , senicapoc showed high CNS penetrance and when administered to rats with peripheral nerve injury, it significantly reversed tactile allodynia similar to the standard of care, gabapentin. In contrast to gabapentin, senicapoc achieved efficacy without any overt impact on locomotor activity. Together, the data demonstrate that the K Ca 3.1 inhibitor senicapoc is effective at reducing mechanical hypersensitivity in a rodent model of peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Friedreich’s Ataxia (FA) is a pediatric neurodegenerative disease whose clinical presentation includes ataxia, muscle weakness, and peripheral sensory neuropathy. The KIKO mouse is an animal model of FA with frataxin deficiency first described in 2002, but neurobehavioral deficits have never been described in this model. The identification of robust neurobehavioral deficits in KIKO mice could support the testing of drugs for FA, which currently has no approved therapy. We tested 13 neurobehavioral tasks to identify a robust KIKO phenotype: Open Field, Grip Strength Test(s), Cylinder, Skilled Forelimb Grasp Task(s), Treadmill Endurance, Locotronic Motor Coordination, Inverted Screen, Treadscan, and Von Frey. Of these, Inverted Screen, Treadscan and Von Frey produced significant neurobehavioral deficits at >8 months of age, and relate to the clinically relevant endpoints of muscle strength and endurance, gait ataxia, and peripheral insensitivity. Thus we identify robust phenotypic measures related to Friedreich's ataxia clinical endpoints which could be used to test effectiveness of potential drug therapy. [ABSTRACT FROM AUTHOR]

The anterior cingulate cortex (ACC) has been extensively cited as a key area for processing pain affect. While local field potential (LFP) studies in other fields have yielded a great deal of information about neural oscillations, there is a poverty in the pain literature about the neural LFP profile related to pain, particularly in freely moving animals. In this study, we revealed the LFP profile in the ACC in freely moving rats during carrageenan inflammation. Mechanical allodynia was recorded before and after unilateral injection of carrageenan/saline in the left hindpaw. LFP activity in the ACC was recorded at baseline, after injection, and after injection with mechanical stimulation to the paw using a von Frey filament. This study uniquely reveals that carrageenan injection significantly recruited ACC LFP activity in delta, theta, and alpha bands (0–13 Hz). Application of von Frey mechanical stimulation to the carrageenan-injected paw resulted in a significant increase in delta, theta, and alpha bands over and above what was recruited by carrageenan alone and further expanded the LFP range to additionally include beta activity (13–30 Hz). Taken together, these data reveal significant changes in the lowest-frequency activities in the LFP range during painful inflammation, which merit attention. LFP is a powerful window to reveal wide-range, integrated synaptic processing by low-frequency cellular events during behavior. Information about LFP during pain broadens the scope of our understanding of pain mechanisms, our greatest resource for designing management approaches. [ABSTRACT FROM AUTHOR]

Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58% for the synergistic doses. The finding of dose-dependent synergistic effects highlights that choosing the right dose–dose combination is of importance in postoperative pain therapy. Our results indicate benefit of high doses of gabapentin as adjuvant to morphine. If these findings translate to humans, they might have important implications for the treatment of pain in postoperative patients. [ABSTRACT FROM AUTHOR]

Aims This study analyzed the sensorial, structural and functional response of rats subjected to paw immobilization. Main methods Animal pelvis, hip, knee and ankle were immobilized using waterproof tape during two weeks for assessment of sensorial response to thermal (hot plate test) and mechanical stimuli (Von Frey test), motor system structure (histology and radiography) and muscle function (soleus contractility). Key findings Disuse animals became more responsive to thermal stimuli (49%), although less responsive to mechanical challenge (58%). Disuse animals showed local injuries such as reduction in muscle fiber diameter (16.7% in gastrocnemius, 5.7% in soleus), contractile activity (55% of the control maximal tonic contraction) and tibia cortical thickness (9.3%), besides increased nitrite:protein ratio, suggestive of protein degradation. Disuse also evoked systemic adaptations that include increase in serum lactate dehydrogenase (36.1%) and alkaline phosphatase (400%), but reduction in calcium (8.4%) and total serum protein (5.5%), especially albumin (34.2%). Significance Two weeks of functional paw disuse leads to local and systemic harmful adaptive changes in sensorial and structural systems. This study brings new insights into nervous and motor system mechanism associated with therapeutic limb immobilization in muscle and skeletal pathological conditions. [ABSTRACT FROM AUTHOR]

Resumo Justificativa e objetivos O fenômeno doloroso é uma das mais importantes e complexas experiências. A fentolamina é antagonista alfa‐adrenérgico não seletivo. O objetivo foi comparar os efeitos de doses crescentes da fentolamina, por via subaracnóidea, em ratos na modulação do fenômeno doloroso. Método Foram usados 84 ratos Wistar machos, divididos nos grupos formalina e incisão plantar, subdivididos em seis subgrupos (n = 7). No subgrupo controle (GC) apenas salina (10 μL), nos subgrupos ativos, 10 μg de fentolamina (GF10), 20 μg (GF20), 30 μg (GF30), 40 μg (GF40) e 50 μg (GF50). No grupo formalina, a dor foi induzida com injeção de 50 μL de formalina a 2%, na região dorsal da pata posterior direita. No grupo incisão plantar, a dor foi induzida por incisão plantar e avaliação pelos filamentos de Von Frey. Indução e manutenção anestésica com halotano a 3% para introdução de cateter no espaço subaracnóideo e feitura da incisão plantar. Análise estatística dos resultados pelo programa JMP do SAS com nível de significância 5%. Resultados A fentolamina nas doses de 20 e 30 μg produziu aumento da resposta álgica na fase intermediária do teste da formalina. No teste da incisão plantar, promoveu efeito hiperálgico no primeiro, terceiro, quinto e sétimo dias na dose de 10 μg, no primeiro, terceiro e quinto dias na dose de 20 μg e no quinto dia na dose de 30 μg. Conclusão A fentolamina por via subaracnóidea promoveu efeito hiperálgico, possivelmente pela participação de diferentes subclasses de receptores alfa‐adrenérgicos nas vias modulatórias da dor. Background and objectives Painful phenomenon is one of the most important and complex experiences. Phentolamine is a non‐selective alpha‐adrenergic antagonist. The objective of this study was to compare the effect of increasing doses of phentolamine into subarachnoid space in rats in the modulation of painful phenomenon. Methods 84 male Wistar rats were divided into formalin and plantar incision groups, subdivided into six subgroups (n = 7). Control group (CG) received only saline (10 μL); active subgroups received phentolamine 10 μmg (GF10), 20 mg (GF20), 30 mg (GF30), 40 mg (GF40), and 50 g (GF50). In formalin group, pain was induced by injection of 50 μL of 2% formalin in dorsal region of right posterior paw. In plantar incision group, pain was induced by plantar incision and evaluated using Von Frey filaments. Induction and maintenance of anesthesia were performed with 3% halothane for catheter placement into subarachnoid space and plantar incision. Statistical analysis was performed using the JMP program from SAS with 5% significance level. Results Phentolamine at doses of 20 and 30 g increased the algesic response in the intermediate phase of the formalin test. In plantar incision test, it had hyperalgic effect on first, third, fifth, and seventh days at a dose of 10 g and on first, third, and fifth days at a dose of 20 g and on fifth day at a dose of 30 g. Conclusion Subarachnoid administration of phentolamine showed hyperalgesic effect, possibly due to the involvement of different subclasses of alpha‐adrenergic receptors in modulating pain pathways. [ABSTRACT FROM AUTHOR]

Spinal nerve L5/L6 ligation (SNL) in rats has become the standard for mechanistic studies of peripheral neuropathy and screening for novel analgesics. Conventional SNL in our hybrid mice resulted in a wide range of allodynia. Anatomical evaluation indicated that a variable number of lumbar vertebrae existed, resulting in L4/L5 or L5/L6 being ligated. Surprisingly, L4/L5 ligation did not result in ipsilateral hind limb paralysis and produced robust allodynia. Following a recent report that the mouse L4 neural segment is homologous with rat L5 we generated L4, L5 or both L4 and L5 (L4/L5) ligations in C57 mice after establishing a modified set of surgical landmarks. In contrast to rats, L4 ligation in these mice did not result in hind limb paralysis. Robust allodynia was observed in all three ligation groups. Nerve degeneration confirmed that L4 and L5, respectively, are primary contributors to the tibial and sural branches of the sciatic nerve in mice. A larger von Frey sensitive area reflected the wider distribution of Wallerian degeneration in the hindlimb of L4- compared to L5-ligated mice. Ligation of mouse L4 and L5 spinal nerves produces consistent, robust neuropathic pain behaviors and is suitable as a model for investigating mechanisms of neuropathic pain and for testing of novel analgesics. Gabapentin, used as a validation drug in neuropathic pain models and as a reference compound for novel analgesics, significantly reduced allodynia in the mice tested (L4/L5 ligations). Given the ease of surgery, robust allodynia, and larger von Frey sensitive area, we conclude that combined ligation of spinal nerves L4 and L5 optimizes the SNL model in mice. [ABSTRACT FROM AUTHOR]

Abstract: Maternal methamphetamine (MA) abuse during pregnancy has been proved to induce various impacts on the development of infant and child. In this study, we examined whether prenatal exposure to MA would affect the development of nociceptive system by measuring the responses to noxious stimulation in the developing rat. Adult female Sprague–Dawley rats received bi-daily subcutaneous injection of methamphetamine (5mg/kg) or isovolumetric normal saline since the day of mating till the day of delivery. Birth profiles of the offspring including birth length, weight, and body temperature were recorded during the first postnatal month. Mechanical withdrawal thresholds were measured by von Frey filaments on postnatal day (PND) 30 and 60, and hyperalgesic behaviors following plantar formalin injection (2%, 50μl) were evaluated on PND 60. The birth body weight and length of rats born to MA-injected dam rats (MA group) were significantly lower than those of the control rats during the first postnatal month; however, their body temperature was significantly higher than those of the control rats during the first 3 days after birth. The MA group rats had significantly lower tactile withdrawal values in von Frey test and higher pain scores in the late phase of pain in the formalin test than those of the control rats. There is a gender difference of nociceptive hypersensitivity manifested as that the female MA group rats had significantly lower withdrawal thresholds and higher pain scores in response to formalin injection than the male MA group rats. These results suggest that prenatal MA exposure could predispose an alteration in the development of nociceptive neuronal network, which leads to a long-lasting status of hypersensitivity to pain stimulations in the offspring. [Copyright &y& Elsevier]

Abstract: The CatWalk gait analysis system has recently been suggested as a rapid and objective alternative method over the von Frey test to assess mechanical allodynia in chronic neuropathic pain models. Our results demonstrate that no correlation exists between the development of mechanical allodynia and changes in CatWalk-gait parameters in a chronic inflammatory pain model. Hence, the use of the CatWalk in assessment of experimental chronic pain is discussed. [Copyright &y& Elsevier]

Abstract: We describe a device which allows the mechanical sensitivity of trigeminovascular sensory neurons to be monitored over extended time periods. The device can be used to stimulate either the skin or dura mater and consists of a solenoid-driven plunger to which are fixed interchangeable von Frey hairs. The solenoid can be attached to a stereotaxic carrier and mounted on a stereotaxic frame to allow precise positioning over the receptive field. The device is driven from the synchronization signals of a standard stimulator via TTL circuitry and a relay driver, to allow stimulation by a single or multiple stimuli. The advantages of the device over manual stimulation include the reproducibility of the site of stimulation; the ability to apply a known force for a known time; the ability to measure response latencies to millisecond precision and to compare them to latencies to other stimuli and; easy interface with computer-control. We discuss some of the drawbacks of the von Frey system as usually used and illustrate the use of the new device with results from experiments on peripherally induced sensitization. [Copyright &y& Elsevier]

Abstract: Tricyclic antidepressants (TCAs) are an important analgesic treatment for neuropathic pain, though the neural substrates mediating these effects are poorly understood. We have used an integrative approach combining behavioural pharmacology with functional magnetic resonance imaging (fMRI) to investigate the effects of chronic treatment with the TCA desipramine, on touch-evoked pain (mechanical allodynia) and brain regional activity in the selective spinal nerve ligation (SNL) model of neuropathic pain. SNL and sham-operated rats received once daily i.p. administration of 10 mg/kg DMI, or saline, for 14 days. Withdrawal responses to the application of a normally non-noxious (10 g) stimulus were recorded in SNL and sham-operated rats over this period. On the final day of the study, SNL and sham-operated rats received a final challenge dose of DMI (10 mg/kg i.p.) during fMRI scanning. Chronic administration of desipramine (DMI) significantly attenuated mechancial allodynia in SNL rats. DMI challenge in chronic DMI-treated neuropathic rats produced significantly greater activation of the deep mesencephalic nucleus, primary somatosensory cortex, insular cortex, medial globus pallidus, inferior colliculus, perirhinal cortex and cerebellum compared to sham-operated rats and saline controls. By contrast, the spatial pattern of brain regional activation by chronic DMI treatment in sham controls encompassed a number of other areas including those associated with learning and memory processes. These novel findings identify key brain regions implicated in the analgesic and mood altering effects associated with chronic treatment with DMI. [Copyright &y& Elsevier]

Abstract: Spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain. However, in recent studies conflicting results regarding the effect of SCS were noted in a selected group of patients suffering from complex regional pain syndrome and mechanical allodynia. In the present study we investigated the pain relieving effect of SCS in a rat experimental model of neuropathic pain as related to the severity of mechanical allodynia. Adult male rats (n=45) were submitted to a unilateral sciatic nerve ligation. The level of allodynia was tested using the withdrawal response to tactile stimuli with the von Frey test. A portion of these rats developed marked tactile hypersensitivity in the nerve-lesioned paw (von Frey test), similar to “tactile allodynia” observed after nerve injury in humans. Prior to SCS treatment the rats were subdivided into three groups based on the level of allodynia: mild, moderate and severe. All allodynic rats were treated with SCS (n=27) for 30 min (f=50 Hz; pulse width 0.2 ms and stimulation at 2/3 of motor threshold) at 16 days post-injury. Our data demonstrate a differential effect of SCS related to the severity of the mechanical allodynia. SCS leads to a faster and better pain relief in mildly allodynic rats as compared with the more severely allodynic rats. Thus, we suggest that the selection and subdivision of patient groups similar to those defined in our experimental setting (mild, moderate and severe allodynic) may provide better pre-treatment prediction of possible therapeutic benefits of SCS. [Copyright &y& Elsevier]

Abstract: Secondary hyperalgesia in the monoarthritic rat is accompanied by a decrease in nociceptive activation of spinal neurons expressing GABAB receptors and by the opposite effect in the cells expressing neurokinin 1 (NK1)-receptors. In order to ascertain the relative role of each receptor, the effects of intrathecal administration of SP-saporin (SP-SAP), baclofen or both were evaluated, using a model of secondary hyperalgesia that consists of mechanical stimulation of the hindlimb skin close to an inflamed joint. Four days after the induction of monoarthritis by intraarticular injection of Complete Freund’s Adjuvant (CFA), a cannula was implanted at T13–L1 level and 10 μl of saline or SP-SAP (10−6 M) were intrathecally (i.t.) injected. Fourteen days after CFA-injection, half of the animals from each group received i.t. injections of 10 μl saline and the remainder were injected with the same volume of baclofen (1 μg). Ten minutes later, the animals were behaviorally evaluated by the von Frey test or submitted to noxious mechanical stimulation to analyze c-fos expression. The von Frey thresholds increased after the treatments, but more pronouncedly after baclofen or SP-SAP plus baclofen. In segments L2–L3, the spinal area that receives input from the stimulated skin close to the inflamed joint, the numbers of Fos-immunoreactive neurons were reduced after the three treatments both in the superficial and deep dorsal horn. In segments T13–L1, the numbers of Fos-immunoreactive neurons were significantly reduced after treatment with SP-SAP plus baclofen in both dorsal horn regions, and in the deep dorsal horn after baclofen treatment. We conclude that both GABAB and NK1 receptors of spinal dorsal horn neurons participate in secondary hyperalgesia in the monoarthritic rat, although the decrease in GABA inhibition appears to play a more important role than the increase in SP-mediated effects. [Copyright &y& Elsevier]

Locomotor and/or sensory behaviour is commonly evaluated in laboratory rats in the field of neuroscience. Many strains of rats, however, have been propagated through intensive breeding programs. With any breeding program, traits are selected purposefully or inadvertently. We set out to investigate whether differences in morphology, sensory or motor behaviours exist using five age-matched strains of laboratory rats. Personal observations of morphological differences between different strains of rats led us to hypothesize that Fischer rats were dissimilar to the other strains in each of the parameters investigated. Evaluation of morphology involved measuring long-bone lengths and body weights of each strain. Motor skills were evaluated by measuring paw preferences while rearing, abduction of the distal portion of hindlimbs during locomotion, footfalls through a horizontal ladder during locomotion, and ground reaction forces generated during trotting. Sensory ability was assessed by von Frey testing. Fischer rats had shorter long-bone lengths, weighed less, and had significantly abducted distal portion of their hindlimbs during locomotion compared to the other strains. Lewis and Sprague–Dawley rats were less sensitive to mechanical pedal stimulation compared to Fischer rats. While rearing, all strains of rats tended to use individual forelimbs 25% of the time for each right and left limbs, and both forelimbs together 50% of the time. There were no significant differences in the number of footfalls during the ladder task. Ground reaction force determination revealed that Fischer and Sprague–Dawley rats bore more weight on their hindlimbs compared to forelimbs during locomotion, Long–Evans and Lewis rats bore more weight on their forelimbs compared to their hindlimbs, while Wistar rats distributed weight evenly between forelimbs and hindlimbs during trotting. We conclude that morphologic, sensory and motor differences exist between the five strains of laboratory rats examined and several of these differences are most pronounced in the Fischer strain. [Copyright &y& Elsevier]

Capparis erythrocarpos is a medicinal plant used widely in many parts of Africa for the management of pain and inflammatory conditions such as rheumatoid arthritis. Its wide range of use, popularity and high value, make C. erythrocarpos containing products a target for economically driven adulteration. This is made worse, by the use of roots, which are unsustainable plant parts. In addition, the mechanism of anti-inflammation is not clearly understood. Therefore, this study comparatively evaluated the anti-arthritic and analgesic effects of the leaves, stems and roots of C. erythrocarpos, while elucidating the mechanism of anti-inflammation. Using the complete Freund's adjuvant arthritis model, the antiathritic effects were evaluated. The analgesic effects were determined by measuring responses to Von Frey filament number 9. Effects of C. erythrocarpos extracts on the levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) were determined using ELISA. Haematological and serum biochemical assays were also carried out. The leaf, stem and root extracts significantly reduced paw volumes with ED 50 values (mg/kg) of 182.5, 181.5 and 36.4 respectively. The leaf extract at a dose of 100 mg/kg showed substantial analgesic activity with a decrease in the percentage response to Von Frey filament 9. However, there was no significant difference in activities of the leaf, stem and root extracts. Results from ELISA assays show that lower doses of the stem extracts reduce levels of IL-6. Lower doses of all extracts also reduce TNF-α levels. Haematological analysis showed extracts reversed elevated WBC and platelet levels. Toxicity evaluation with kidney and liver function tests indicated no significant differences between the treatment and control groups. The leaves and stems, just as the roots, have antiarthritic and analgesic effects and can be used as more sustainable alternatives to the roots. This will support the continuous growth of the industry that has developed around C. erythrocarpos. Image 1 [ABSTRACT FROM AUTHOR]