Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography

Regional cerebral blood flow was measured with positron emission tomography (PET) in six healthy volunteers at rest and during experimentally induced, sustained cutaneous pain on the dorsum of the right hand or on the dorsum of the right foot. Pain was inflicted by intracutaneous injection of capsaicin, providing a mainly C-fibre nociceptive stimulus. Statistical analysis showed significant activations along the central sulcus (SI) area when comparing pain in the hand to pain in the foot. Separate comparison of both pain states to a baseline revealed different locations along the central sulcus for hand pain and foot pain. The encountered differences are consistent with what is previously known about the somatotopics of non-painful stimuli. When comparing painful stimuli to baseline, the contralateral anterior cingulate gyrus, the ipsilateral anterior insular cortex and the ipsilateral prefrontal cortex were implicated. The results are consistent with an involvement of SI in the spatial discrimination of acute cutaneous pain. Received: 17 October 1996 / Accepted: 12 May 1997     

Human cerebral potentials evoked by CO2 laser stimuli causing pain

Summary Brief radiant heat pulses, generated by a CO₂ laser, were used to activate slowly conducting afferents in the hairy skin in man. In order to isolate C-fibre responses a preferential A-fibre block was applied by pressure to the radial nerve at the wrist. Stimulus estimation and evoked cerebral potentials (EP), as well as reaction times, motor and sudomotor activity were recorded in response to each stimulus. With intact nerve, the single supra-threshold stimulus induced a double pain sensation: A first sharp and stinging component (mean reaction time 480 ms) was followed by a second burning component lasting for seconds (mean reaction time 1350 ms). Under A-fibre block only one sensation remained with characteristics and latencies of second pain. The heat pulse evoked potential consisted of a late vertex negativity at 240 ms (N240) followed by a prominent late positive peak at 370 ms (P370). Later activity was not reliably present. Under A-fibre block this late EP was replaced by an ultralate EP beyond 1000 ms, which in the conventional average looked like a slow halfwave of 800 ms duration. This potential was distinct from eye movements, skin potentials or muscle artefacts. With cross-correlation methods waveforms similar to the N240/P370 were detected in the latency range from 900 to 1500 ms during A-fibre block, indicating a much greater latency jitter of the ultralate EP. Latency corrected averaging with a modified Woody filter yielded a grand mean ultralate EP (N1050/P1250), the shape of which was surprisingly similar to the late EP (N240/P370). The similarity of these components indicates that both EPs may be secondary responses to afferent input into neural centers, onto which myelinated and unmyelinated fibres converge. Such convergence may also explain through the known mechanisms of short term habituation and selective attention, why ultralate EPs are not reliably present without peripheral nerve block.     

大鼠三叉神经节内含内吗啡肽2的神经元向延髓背角投射

目的 观察大鼠三叉神经节(TG)内的内吗啡肽2(EM2)阳性神经元向延髓背角(MDH)的投射情况.方法 荧光金(FG)追踪与EM2免疫荧光组织化学染色相结合的双标方法.结果 将FG注入MDH后,TG内可见大量FG标记的大、中、小型神经元;TG内也可见各种直径的EM2阳性神经元;TG内的许多FG标记神经元呈EM2阳性,FG/EM2双标神经元多为中、小型神经元.结论 TG内的EM2阳性神经元向MDH投射.     

Changes in extracellular potassium concentration in cat spinal cord in response to innocuous and noxious stimulation of legs with healthy and inflamed knee joints

Summary In 20 cats anaesthetized with alpha-chloralose and spinalized at the thoracolumbar junction we investigated the role of stimulation induced accumulation of extracellular potassium in the spinal cord in the processing of nociceptive discharges from the knee joint. For that we electrically stimulated the posterior articular nerve of the knee. We further performed innocuous and noxious stimulation of the knee and of other parts of the leg and studied the effect of an acute inflammation of the knee on [K⁺]₀ in the spinal cord. Innocuous stimulation of the skin (brushing or touching) and innocuous movements in the knee joint all induced rises in [K⁺]₀ which were maximal at recording depths of 1500 to 2200 m below the surface of the cord dorsum. Peak increases were 0.4 mM for touching the leg and 1.7 mM during rhythmic flexion/ extension of the knee joint. Noxious stimulation of the skin, the paw, the tendon and noxious movements of the knee joint also produced rises in [K⁺]₀, which were somewhat larger for the individual types of stimuli than those produced by innocuous intensities. Electrical stimulation of the posterior articular nerve induced rises in [K⁺]₀ by up to 0.6 mM. Stimulus intensities sufficient to activate unmyelinated group IV fibers were only slightly effective in raising [K⁺]₀ above the levels reached during stimulation of myelinated group II and III fibers. During development of an acute inflammation of the knee joint (induced by kaolin and carrageenan), increases in [K⁺]₀ and associated field potentials became larger by about 25%. We assume that this reflects an increase in neuronal responses. In conclusion, changes in [K⁺]₀ in the spinal cord are some-what larger during noxious stimulation than during innocuous stimulation. The absolute level reached depended more on the site and type of stimulation than on the actual stimulus intensity itself. Hence a critical role of spinal K⁺ accumulation for nociception is unlikely.     

非营养性吸吮联合音乐治疗对新生儿疼痛的缓解作用

目的观察非营养性吸吮（NNS）、音乐治疗（MT）及非营养性吸吮联合音乐治疗（NNS＋MT）在缓解新生儿疼痛中的作用。方法收集2008年1～6月在南京医科大学附属南京儿童医院新生儿医学中心普通新生儿病房收治的新生儿作为研究对象,对符合纳入和排除标准的新生儿按照住院号从小到大顺序分为干预组（NNS亚组、MT亚组、NNS＋MT亚组）和空白对照组,干预措施在新生儿足后跟采血前2min开始持续至研究结束,共15min,空白对照组不予干预措施。通过观察新生儿的心率、经皮氧饱和度（SpO2）及新生儿疼痛行为（NIPS）评分,采集采血针刺前1min、针刺时和针刺后13min过程中的每一分种数据,比较各种干预措施缓解新生儿疼痛的临床效果。采用SPSS11.0软件进行多变量方差分析,ANOVA方差检验,同时应用PostHoc进行组间比较。结果纳入住院新生儿80例,男54例,女26例;各亚组和空白对照组各20例。疼痛刺激后各组的心率均显著加快,于刺激后0～2min达峰值,之后逐渐减慢;NNS亚组与空白对照组心率差异无统计学意义,MT、NNS＋MT亚组与空白对照组心率差异均有统计学意义,MT亚组和NNS＋MT亚组心率差异无统计学意义。疼痛刺激后各亚组SpO2均显著降低,于刺激后2～4min降至最低值,之后逐渐升高;NNS亚组与对照组SpO2差异无统计学意义,MT、NNS＋MT亚组与空白对照组SpO2差异均有统计学意义,MT亚组和NNS＋MT亚组SpO2差异无统计学意义。疼痛刺激后各组NIPS评分均显著提高,于0～1min达峰值,之后逐渐降低,各亚组NIPS评分差异均无统计学意义。与空白对照组比较,MT、NNS＋MT干预措施均可缓解疼痛刺激引起的心率、SpO2和NIPS评分变化。结论新生儿临床医护人员可通过使用MT和NNS＋MT可缓解新生儿疼痛。     

Convergent inputs from articular,cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord

Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (s cells), 17 neurones excited by receptors in deep tissues (d cells), 15 units with a convergent input from receptors in skin and deep tissues (sd cells), and 25 neurones with a convergent input from the knee joint and either skin (sj cells), deep tissues (dj cells) or both (sdj cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. S and sj cells were found almost exclusively in the dorsal horn, whereas many d, sd, sdj and dj units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (sj cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (sdj cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 dj cells, the receptive fields included not only the knee joint but also deep fields like those of sdj cells. 6. Cutaneous receptive fields were classified as low threshold (cells excited best by innocuous intensities of mechanical stimulation), wide dynamic range (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice

In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 g) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 g) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat.