ABSTRACT
Aim To investigate the role of collybistin in the regulation of pain transmission. Methods The distribution of collybistin in spinal cord was observed by immunohistochemical staining. The role of collybis¬tin in pain transmission was evaluated by behavioral experiments. The effect of collybistin on inhibitory synap¬tic transmission was studied by electrophysiological ex¬periments. Results Collybistin was distributed in spi¬nal cord neurons; ShRNA-collybistin induced pain sen-sitization of intact mice ( P < 0. 05 ) . Overexpression of collybistin in spinal cord significantly alleviated pain sensitization induced by peripheral nerve injury ( P <0. 05 ) . ShRNA-collybistin also significantly reduced the amplitudes and frequencies of miniature inhibitory postsynaptic currents (mlPSCs) in superficial neurons of spinal cord dorsal horn (P <0. 05) . Overexpression of collybistin in spinal cord could reverse the effects of peripheral nerve injury on mlPSCs (P <0. 05). Con¬clusions Collybistin is involved in pain sensitization induced by peripheral nerve injury in mice.
ABSTRACT
Pathological pain or clinical pain is caused by tissue and nerve injuries, and is usually chronic and mainly divided into inflammatory pain and neuropathic pain. Pathological pain is typically characterized by hyperalgesia (increased responsiveness to noxious stimuli) and allodynia (painful responses to normally innocuous stimuli). The mitogen-activated proteins kinases (MAPKs) are a family of evolutionally conserved molecules that play a critical role in cell signaling, consisting of extracellular signal regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), which play an important role in neural plasticity of pathological pain. Inhibition of MAPKs alleviates inflammatory pain and neuropathic pain in different animal models. It is very important to study the inhibition of MAPKs as a therapeutic approach to treat pathological pain.
ABSTRACT
BACKGROUNDS: Pain can occur following acute noxious stimuli and tissue damage. The duration of such pain may outlast the stimulus and its amplitude may be exaggerated (hyperalgesia). This response comes from a sensitization of the peripheral nociceptor. Traditional thought has associated the antinociceptive effects of opiates with the activation of opioid receptors located in the central nervous system. Recently, however, opiate receptors in the peripheral nervous system have led to the hypothesis that analgesic action might, in part, result from a reduction in the response of peripheral nerve fibers thought to be concerned with signaling pain. METHODS: Twenty units were recorded from the strands of the hypogastric nerve innervating the urinary bladder of the cat. Nerve activity and intravesical pressure were monitored before and after the onset of an acute inflammation induced by the intravesical instillation of 2% mustard oil. The responses of afferent units to chemical stimuli by intra-arterially injected bradykinin (10 microgram/0.2 ml., i.a.) and potassium chloride (0.3 M/0.2 ml, i.a.) were compared each time at control, after inflammation, and after administration of morphine (2.5 mg/kg) and naloxone (5 microgram/kg) respectively. RESULTS: Polymodal receptors in the urinary bladder showed excitatory response to algesic substances such as bradykinin, potassium chloride and the urinary bladder contracted simultaneously, both the responses of the nerve impulse and bladder contraction to bradykinin and potassium chloride increased significantly after bladder inflammation induced by 2% mustard oil and the sensitization of the sensory receptors attenuated by morphine and naloxone reversed the effect of morphine. CONCLUSIONS: These observations suggest that morphine might have a peripheral effect.