Articles: hyperalgesia.
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Preclinical research for neuropathic pain has depended primarily on the use of behavioural nociceptive testing that is sensory-discriminatory-based and reflexive in nature. This can be particularly problematic in spinal cord injury (SCI)-associated neuropathic pain research where hyperreflexia may develop thus confounding interpretation of reflexive responses as pain symptoms. To address this, we have designed an affective-motivational-based Overground System that has interchangeable floors to allow examination of nociceptive behaviours in response to mechanical and cold stimuli prior to and following spinal cord injury. ⋯ We have designed an Overground System that is easy to establish and addresses a major concern in preclinical pain research by providing a cognitive- and motivational-based system for hypersensitivity detection. The affective-motivational-based Overground System allows examination of pain-like behaviours in response to cold (thermal) and rough (mechanical) stimulation prior to and following spinal cord injury. This system provides a more holistic and comprehensive assessment of nociceptive responses following SCI and helps overcome concerns of hyperreflexia confounding-evoked behavioural outcome measures in SCI models. Further, the incorporation of cognitive and motivational components brings preclinical research closer to replicating the clinical experience of a patient's motivation to participate in rewarding lifestyle activities in relation to their pain.
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Chemotherapy-induced neuropathic pain is a common dose-limiting side effect of anticancerdrugs but lacks an effective treatment strategy. Scolopendra subspinipes has been used in traditional medicine to treat chronic neuronal diseases. Moreover, pharmacopuncture with S subspinipes (SSP) produces potent analgesia in humans and experimental animals. ⋯ The combination of SSP with a lower dose of clonidine (0.03 mg/kg) produced a comparable analgesic effect without side effects. Collectively, our findings demonstrate that SSP produces an analgesic effect in oxaliplatin-induced pain via neuronal conduction at the acupoint and activation of spinal α2-adrenoceptors. Moreover, acombination of low-dose clonidine with SSP represents a novel and safe therapeutic strategy for chemotherapy-induced chronic pain.
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Sickle cell disease (SCD) is a genetic blood disorder that impacts millions of individuals worldwide. SCD is characterized by debilitating pain that can begin during infancy and may continue to increase throughout life. This pain can be both acute and chronic. ⋯ Thus, pain management in SCD remains a major challenge. Humanized transgenic mice expressing exclusively human sickle hemoglobin show features of pain and pathobiology similar to that in patients with SCD. Therefore, these mice offer the potential for investigating the mechanisms of pain in SCD and allow for development of novel targeted analgesic therapies. © 2018 by John Wiley & Sons, Inc.
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Neuroscience letters · Sep 2018
The left central nucleus of the amygdala contributes to mechanical allodynia and hyperalgesia following right-sided peripheral nerve injury.
The left and right central nucleus of the amygdala (CeA) exert asymmetric pronociceptive functions. In the setting of a transient noxious stimulus or persistent inflammatory pain, neuronal activity increases in the right but not left CeA, regardless of side of injury. Much less is known regarding this lateralization with respect to the behavioral manifestations of persistent neuropathic pain. ⋯ Following right-sided SNI, we observed a modality-dependent effect: mechanical allodynia was attenuated by inactivation of the left but neither the right nor bilateral CeA, mechanical hyperalgesia was attenuated by left, right and bilateral intra-CeA lidocaine, and cold allodynia was unaffected. These data suggest that CeA-mediated control of neuropathic pain is not strictly limited to the right CeA as previously assumed. We conclude that functional lateralization depends on the type of pain, side of injury and the sensory modality, and that the left CeA contributes to mechanical allodynia and hyperalgesia after peripheral nerve injury to the right side of the body.
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Neuroligin 1 (NLGN1), a cell adhesion molecule present at excitatory glutamatergic synapses, has been shown to be critical for synaptic specialization and N-methyl-d-aspartate (NMDA)-subtype glutamate receptor-dependent synaptic plasticity. Whether and how NLGN1 is engaged in nociceptive behavioral sensitization remains largely unknown. In this study, we found an activity-dependent regulation of NLGN1 synaptic expression in pain-related spinal cord dorsal horns of mice. ⋯ We also found that one of the important roles of NLGN1 was to facilitate the clustering of NMDAR at synapses. The NLGN1-targeting siRNA suppressed the synaptic expression of GluN2B-containing NMDAR in CFA-injected mice and meanwhile, attenuated the inflammatory mechanical allodynia and thermal hypersensitivity. These data suggested that tissue injury-induced synaptic redistribution of NLGN1 was involved in the development of pain hypersensitivity through facilitating the synaptic incorporation of NMDARs.