猫皮层体感区躯体伤害感受神经元的电生理特征

应用细胞内记录技术,观察了皮层体感区1576个神经元对伤害性刺激隐神经的诱发反应。电刺激隐神经在SI区伤害感受神经元可引起兴奋性反应、抑制性反应和兴夯与抑制混和性反应三种,吗啡可抑制伤害感受神经元的诱发反应。完成电生理观察后对部分神经元电泳神经生物素进行细胞内形态标记。可见,伤害感受神经与元非伤害感受神经元电生理特性不同,形态特征也存在着差异。此结构在细胞水平为进一步探讨皮层体感区在痛觉感受及调中的作用奠定了基础。     

大鼠口舌部粘膜伤害性刺激信息的感受及传导通路

本文采用以辣根过氧化物酶（ＨＲＰ）注入丘脑腹后内侧核区的逆行追踪技术结合用盐酸溶液刺激大鼠口、舌粘膜的方法，观察了ＦＯＳ、ＨＲＰ单标记和双标记神经元在三叉神经脊束核尾侧亚核内的分布．证明脑干内除臂旁核、孤束核、延髓腹外侧网状结构等脑区外，大量ＦＯＳ样阳性神经元聚集于三叉神经尾侧亚核Ⅰ、Ⅱ层，三叉旁核（间质核）有中等量分布而Ⅳ、Ⅴ层内仅见散在标记细胞．ＨＲＰ逆行标记细胞主要位于注射对侧的三叉神经感觉主核和脊束核．三叉神经尾侧亚核内的逆行标记细胞局限于背外侧部Ⅰ层，多为沿外缘呈切线方向走行的圆形、椭圆形和梭形细胞．在三叉神经脊束核尾侧亚核背外侧部浅层内，可见到一些胞浆内含ＨＲＰ反应产物、核为ＦＯＳ样阳性的双标记神经元．本文结果提示三叉神经尾侧亚核浅层内存在大量对口、舌粘膜伤害性刺激起反应的痛感受神经元，其中部分神经元将伤害性感觉传入信息传递至丘脑．     

动脉血压对缰核放电的影响

静脉注射去甲肾上腺素使血压升高,引起大鼠缰核自发放电增多,静注硝普钠使血压下降,引起缰核自发放电减少。用吗啡或芬太尼后,对自然痛刺激的痛反应—缰核放电频率增高消失,但去甲肾上腺素引起缰核放电增多效应仍然出现。提示缰核与心血管活动调节有关。     

酚妥拉明阻断去甲肾上腺素对大鼠束旁核痛反应神经元电活动的影响

目的：去甲肾上腺素及其α受体阻断剂酚妥拉明对大鼠束旁核痛反应神经元电活动的影响。方法：以串刺激右侧坐骨神经为伤害性刺激，用玻璃微电极细胞外记录大鼠束旁核痛反应神经元电活动。结果：脑室去甲肾上腺素抑制旁核束旁核痛兴奋神经元放电，促进痛抑制神经元放电，此作用可被酚妥拉明阻断。结论：酚妥拉明阻断去甲肾上腺素对大鼠束旁核痛反应神经元电活动的抑制作用，提示去甲肾上腺素的镇痛作用与α肾上腺素能受体关系密切。     

内脏和躯体初级传入冲动在猫骶髓后连合核的汇聚

用玻璃微电极细胞外记录的方法，观察了在电刺激猪盆神经和胫神经或机械性刺激会阴部时骶髓后连合核神经元自发放电频率的变化．共记录了80个单位放电神经元，其中13个为无关单位．电反应类型有3种：长潜伏期长串反应，短潜伏期长串反应，抑制性反应．在所观察的对刺激呈有效反应的67个单位中，30个（44．78％）对躯体和内脏刺激均起反应，其中，12个对盆神经和胫神经传入冲动都起反应；18个对盆神经和会阴部躯体感受野的传入呈汇聚性反应．对会阴部感受野施加各种机械性刺激，鉴定此汇聚神经元为WDR神经元．67个有效反应单位中还有5个（7.46％）只对内脏传入冲动，32个（47.76％）仅对躯体传入冲动做出反应．本研究从电生理学上验证了本教研室在形态学上发现的盆腔内脏（膀胱）初级传入和坐骨神经躯体初级传入在骶髓后连合核神经元的汇聚，并对汇聚的类型和意义进行了观察和讨论．     

一氧化氮合酶阳性结构在大鼠三叉神经感觉核簇内的分布及其与面部伤…

用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶组织化学技术与ＦＯＳ免疫组化（ＡＢＣ法）相结合的方法，观察了大鼠三叉神经感觉核簇内一氧化氮合酶阳性神经元和纤维的分布及其与面部伤害性刺激诱发的ｃ－ｆｏｓ原癌基因蛋白表达的关系。证明，浓密的一氧化氮合酶阳性纤维和终末分布于三叉神经脊束核尾侧亚核的Ｉ和Ⅱ层，阳性成分呈蓝黑色的带状分布，而在三叉神经感觉核簇的其余核区内很稀疏。一氧化氮合酶阳性神经元胞体与面部伤害性刺激     

大鼠延髓内神经激肽B受体神经元对腹膜伤害性刺激的Fos表达——免疫组织化学双重染色研究

为探讨神经激肽Ｂ受体（ｎｅｕｒｏｋｉｎｉｎｂｒｅｃｅｐｔｏｒ，ＮＫＲ）神经元在大鼠延髓的定位及其在腹膜伤害性传入信息整合中的作用。应用免疫组织化学双重染色方法，显示ＮＫＲ神经元的分布并观察它们对腹膜化学伤害性刺激的Ｆｏｓ表达。结果表明：ＮＫＲ样免疫反应（ＮＫＲ－ＬＩ）神经元主要分布在孤束核（Ｓｏｌ）、延髓腹外侧区（ＶＬＭ）、三叉神经脊束核尾侧亚核（Ｓｐ５Ｃ）浅层和三叉旁核（Ｐａ５）。腹膜伤害性刺激激诱导的Ｆｏｓ表达神经元多数分布在Ｓｏｌ、ＶＬＭ、Ｐａ５和最后区。Ｓｏｌ、ＶＬＭ和Ｐａ５中约３０．１％的ＮＫＲ－ＬＩ神经元同时呈Ｆｏｓ样免疫反应。本研究提示：延髓内上述核团ＮＫＲ－ＬＩ神经元与腹膜伤害性初级传入信息的整合有关，可能参与内脏伤害性刺激的抗伤害性感受（ａｎｔｉ－ｎｏｃｅｃｉｐｔｉｏｎ）过程。     

大鼠三叉神经领域伤害性刺激引起的脑内FOS阳性神经元出现规律与分布特征

将福尔马林注射到大鼠上唇左侧口周区皮下,大鼠脑内Fos样神经元的出现及分布具有明显的时间及空间特异性。Fos样神经元在中枢神经系统内的最早出现时间是注射后30min;1h达到高峰;2h后Fos样神经元数量开始下降;8h后,仅在缰核内尚有少量的Fos样神经元分布,这种状态一直持绩到72h。实验结果提示,中枢神经系统参与伤害性刺激的传递及调节的结构既包括特异性的传导通路也包括一些对伤害性刺激的调节有关的结构。本实验又在注射福尔马林前30min给大鼠皮下注射吗啡,然后将10％福尔马林注射到大鼠上唇左侧口周区皮下,1h后发现Fos样神经元的出现受到明显的抑制,但Fos样神经元的分布状况与单纯注射福尔马林者相同。又在注射福尔马林前35min给大鼠皮下注射纳络酮,前30min给大鼠皮下注射吗啡,然后将福尔马林注射到左侧大鼠口周区皮下,1h后发现纳络酮将吗啡对Fos样神经元出现的抑制作用翻转,且Fos样神经元的分布状况与单纯注射福尔马林者相同。这一现象说明Fos的表达与痛觉有关。     

内脏伤害性刺激诱导的大鼠延髓内Fos表达

用抗Ｆｏｓ蛋白和酷氨酸羟化酶（ＴＨ）的免疫组织化学方法，对大鼠两种内脏伤害性刺激诱导的大鼠延髓Ｆｏｓ表达情况及其与儿茶酚胺能神经元的关系进行了观察。提示延髓内脏带半数以上的儿茶酚胺神经元参与对内脏伤害性刺激的反应。     

刺激中缝大核对伤害性刺激内脏大神经引起的猫海马单位放电的影响

猫海马(HPC)结构存在着痛相关神经元,它他的活动可被针刺和外源性吗啡所抑制。刺激内脏大神经可以在背侧 HPC 记录到波形稳定的诱发电位。中缝大核(NRM)是脑内的重要抗痛结构之一、是5—HT 神经元的主要集中地。其发出的纤维可达到 HPC。本工作以伤害性刺激内脏大神经观察 HPC 单位的反应以及刺激 NRM 后的变化、从而探讨 HPC 与内脏     

Mechanical stimulation activates small fiber mediated nociceptive responses in the nucleus gigantocellularis

We characterized nociceptive discharges induced by mechanical stimulation and the modulating effects of orphanin FQ on noxious responses in the rat brain stem gigantocellular reticular nucleus (Gi). A pressure pulse of constant force and rising rate was delivered by a mechanical stimulator with feedback control, allowing responses to be analyzed statistically. A pressure pulse of 300 g, which evoked C-fiber mediated nerve responses, was delivered to the tail. Two excitatory (45/58) and one inhibitory (13/58) types of extracellular unit discharges were recorded in Gi. One of the excitatory types was a phasic discharge (13/45) elicited at the onset and/or the end of stimulation. Latencies of the phasic discharges (0.104±0.1 s) were shorter than those of other type (tonic) discharges (0.43±0.2 s). The tonic discharges (32/45), which frequently persisted past the end of stimulation without adaptation, were classified into two groups. The first group of tonic type units (23/45) was high threshold, like nociceptive specific neurons in the primary sensory cortex, while the second group of neurons (9/45) responded to a wide range of stimulus intensities. The mean frequency, response duration and spike numbers gradually increased with stimulus intensity change in all nine neurons. The neurons encode mechanical stimulus intensity with discharge frequency, response duration and evoked spike numbers. Local injection of orphanin FQ (200 ng/2 μl) changed high threshold tonic type spike numbers in a biphasic manner, i.e., there was an early phase suppression (5–30 min, p=0.016) and a late phase enhancement (30–60 min, p=0.027). In contrast, phasic type discharges did not show an altered discharge pattern in response to orphanin FQ. Thus, orphanin FQ affects small fiber-mediated nociceptive responses and may behave as a complex modulator of pain systems in the brain stem. Electronic Publication     

Selective inhibition of glucose-sensitive neurons in rat lateral hypothalamus by noxious stimuli and morphine

On the basis of their responsiveness to electrophoretically applied glucose, neurons in the lateral hypothalamic area (LHA) have been characterized as either glucose sensitive or glucose nonsensitive. Glucose-sensitive neurons are important in feeding control (4, 36-38, 44, 54). The aim of this study was to increase understanding of the neurophysiological mechanisms involved in the disturbance of feeding by pain. Radiant heating of the scrotum, strong tail pinch, and immersion of the tail in hot water were used as noxious stimuli. In order to correlate the responses of LHA neurons to noxious inputs with possible local release of endogenous opiates, effects of electrophoretically applied morphine and naloxone were also tested. The effects of glucose, morphine, and noxious stimulation were studied in a total of 165 neurons recorded from 75 adult male urethane-chloralose-anesthetized rats. Of 52 neurons determined to be glucose sensitive, 36 (69%) were inhibited by both noxious stimulation and morphine. A majority of the glucose-nonsensitive neurons did not respond to either morphine or noxious stimulation (87/113, 74%). The relation of glucose sensitivity to inhibition by pain and/or morphine was statistically significant (Fisher's exact probability test, P less than 0.01). Naloxone attenuated the inhibitory effects of both pain and morphine, thus suggesting mediation of both by the same neuronal mechanism. From this evidence we conclude that LHA glucose-sensitive neurons are involved in the suppression of feeding by noxious stimulation.     

Discharge patterns of afferent cutaneous nerve fibers from the rat's tail during prolonged noxious mechanical stimulation

Summary Feedback controlled constant force stimuli of 4, 6 and 8 N intensities and of 120 s duration were applied to the receptive fields of cutaneous afferent fibers in the rat's tail. Two types of nociceptive units showed sustained discharges during these stimuli: polymodal unmyelinated C-units (MH-C units, N = 18, c.v. 0.5–0.9 m/s) and high-threshold mechanoreceptive A-delta-units(HTM-units, N=10, c.v. 1.9–11.2 m/s). In addition two classes of sensitive low threshold mechanoreceptors, SA I (N=6) and SA II (N=5) units, responded to the prolonged mechanical stimuli. At the onset of a noxious pressure, 11 of the 18 polymodal nociceptors exhibited dynamic responses (lasting about 10 s) which were followed by slowly adapting tonic discharges that lasted for the duration of the stimuli. The remaining polymodal C-fiber units (8/18) did not show dynamic discharges at 4 and 6 N. Phasic and tonic discharges were positively correlated with stimulus strength. The HTM-units encoded stimulation intensity mainly by their dynamic discharges. The tonic discharges of these units displayed faster adaptation rates with stronger mechanical stimuli, i.e. encoding of stimulation intensity became progressively weaker during the tonic phase. The discharges of sensitive SA I and SA II units with A beta axons were not positively correlated with the strength of noxious pressure stimuli. Tonic discharge rates of SA I units were negatively correlated to stimulus strength, whereas SA II units usually stopped firing in the course of a stimulus and became reversibly irresponsive to mechanical stimulation. Possible afferent mechanisms underlying the induction of pain by sustained noxious mechanical stimulation are discussed.     

Superficial dorsal horn neurons identified by intracutaneous histamine: chemonociceptive responses and modulation by morphine

We have investigated whether neurons in superficial laminae of the spinal dorsal horn respond to intracutaneous (ic) delivery of histamine and other irritant chemicals, and thus might be involved in signaling sensations of itch or chemogenic pain. Single-unit recordings were made from superficial lumbar dorsal horn neurons in pentobarbital sodium-anesthetized rats. Chemoresponsive units were identified using ic microinjection of histamine (3%, 1 microl) into the hindpaw as a search stimulus. All superficial units so identified [9 nociceptive-specific (NS), 26 wide-dynamic-range (WDR)] responded to subsequent ic histamine. A comparison group of histamine-responsive deep dorsal horn neurons (n = 16) was similarly identified. The mean histamine-evoked discharge decayed to 50% of the maximal rate significantly more slowly for the superficial (92.2 s +/- 65.5, mean +/- SD) compared with deep dorsal horn neurons (28. 2 s +/- 11.6). In addition to responding to histamine, most superficial dorsal horn neurons were also excited by ic nicotine (22/25 units), capsaicin (21/22), topical mustard oil (5/6), noxious heat (26/30), and noxious and/or innocuous mechanical stimuli (except for 1 unit that did not have a mechanosensitive receptive field). Application of a brief noxious heat stimulus during the response to ic histamine evoked an additive response in all but two cases, followed by transient depression of firing in 11/20 units. Intrathecal (IT) administration of morphine had mixed effects on superficial dorsal horn neuronal responses to ic histamine and noxious heat. Low morphine concentrations (100 nM to 1 microM) facilitated histamine-evoked responses (to >130% of control) in 9/24 units, depressed the responses (by >70%) in 11/24, and had no effect in 4. Naloxone reversed morphine-induced effects in some but not all cases. A higher morphine concentration (10 microM) had a largely depressant, naloxone-reversible effect on histamine responses. Responses of the same superficial neurons to noxious heat were facilitated (15/25), reduced (8/25), or unaffected (2/25) by low morphine concentrations and were depressed by the higher morphine concentration. In contrast, deep dorsal horn neuronal responses to both histamine and noxious heat were primarily depressed by low concentrations of morphine in a naloxone-reversible manner. These results indicate that superficial dorsal horn neurons respond to both pruritic and algesic chemical stimuli and thus might participate in transmitting sensations of itch and/or chemogenic pain. The facilitation of superficial neuronal responses to histamine by low concentrations of morphine, coupled with inhibition of deep dorsal horn neurons, might underlie the development of pruritis that is often observed after epidural morphine.     

Cardiovascular and neuronal responses to head stimulation reflect central sensitization and cutaneous allodynia in a rat model of migraine

Reduction of the threshold of cardiovascular and neuronal responses to facial and intracranial stimulation reflects central sensitization and cutaneous allodynia in a rat model of migraine. Current theories propose that migraine pain is caused by chemical activation of meningeal perivascular fibers. We previously found that chemical irritation of the dura causes trigeminovascular fibers innervating the dura and central trigeminal neurons receiving convergent input from the dura and skin to respond to low-intensity mechanical and thermal stimuli that previously induced minimal or no responses. One conclusion of these studies was that when low- and high-intensity stimuli induce responses of similar magnitude in nociceptive neurons, low-intensity stimuli must be as painful as the high-intensity stimuli. The present study investigates in anesthetized rats the significance of the changes in the responses of central trigeminal neurons (i.e., in nucleus caudalis) by correlating them with the occurrence and type of the simultaneously recorded cardiovascular responses. Before chemical stimulation of the dura, simultaneous increases in neuronal firing rates and blood pressure were induced by dural indentation with forces >/= 2.35 g and by noxious cutaneous stimuli such as pinching the skin and warming > 46 degrees C. After chemical stimulation, similar neuronal responses and blood pressure increases were evoked by much smaller forces for dural indentation and by innocuous cutaneous stimuli such as brushing the skin and warming it to >/= 43 degrees C. The onsets of neuronal responses preceded the onsets of depressor responses by 1.7 s and pressor responses by 4.0 s. The duration of neuronal responses was 15 s, whereas the duration of depressor responses was shorter (5.8 s) and pressor responses longer (22.7 s) than the neuronal responses. We conclude that the facilitated cardiovascular and central trigeminal neuronal responses to innocuous stimulation of the skin indicate that when dural stimulation induces central sensitization, innocuous stimuli are as nociceptive as noxious stimuli had been before dural stimulation and that a similar process might occur during the development of cutaneous allodynia during migraine.     

Atypical on-, off- and neutral cells in the rostral ventromedial medulla oblongata in rat

It is generally assumed that the response pattern of on-, off- and neutral cells in the rostral ventromedial medulla (RVM) to noxious stimulation is independent of stimulation site. But recent studies have shown that a remarkable number of RVM neurons do not have whole-body receptive fields. These so-called atypical neurons were extracellularly recorded in lightly anaesthetized rats. The receptive fields to noxious thermal and mechanical stimulation applied to the tail, the extremities and the craniofacial region were determined in 57 RVM neurons. In 24 atypical off-cells, 12 on-cells and 21 neutral cells, the response pattern evoked by noxious pinch to the nose, forehead and ear most frequently differed from the responses to noxious tail heat. The modulatory effects of intravenously administered morphine were examined in 21 cells. In contrast to the general assumption that morphine activates off-cells, inhibits on-cells and has no effect on neutral cells, in atypical RVM neurons 5 of 6 off-cells, 2 of 6 on-cells and 5 out 9 neutral cells showed a different response pattern to systemical administration of morphine. The results show that a RVM cell classification that is exclusively based on the behaviour to noxious tail heat can neither sufficiently predict the response pattern to different noxious stimuli, especially in the craniofacial region, nor reliably predict the modulatory effect of morphine in RVM neurons. The fact that the neutral cells responded in an off or on manner to noxious stimulation different from noxious tail heat and that morphine modulated activity in many neutral cells suggests that these cells are probably subtypes of on- and off-cells.     

Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats

Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for >/=7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.     

Effects of a carrageenan-induced myositis on the discharge properties of group III and IV muscle receptors in the cat

1. To see how muscle group III and IV receptors are affected by a myositis, the background activity and mechanical excitability of slowly conducting afferent units from normal and inflamed muscles were studied in chloralose-anesthetized cats. The inflammation was induced by infiltrating the gastrocnemius-soleus muscle with a suspension of 2% carrageenan. According to their responsiveness to local pressure stimulation the receptors were classified as touch units, moderate pressure units, and noxious pressure (probably nociceptive) units. The impulse activity in single afferent units was recorded up to 14 h after induction of the inflammation. 2. In inflamed muscle both group III and group IV receptors showed an increase in the proportion of units having a background activity and in the mean background activity. The differences reached statistically significant levels in group III fibers only. 3. A characteristic feature of the background activity of some receptors in inflamed muscle was its intermittent nature: the discharges occurred either as grouped impulses of short duration or as phases of relatively high discharge frequency alternating with long periods of silence. 4. In normal muscle no receptor exhibited intermittent discharges or had a discharge rate exceeding 7 imp/min. Thus the presence of an intermittent background activity or a high frequency of the background discharge can be considered as characteristic for afferent units from an inflamed muscle. 5. The time course of the background activity showed two peaks, one occurring 2-4 h, the other one 6-7 h after induction of the inflammation. Recordings of single units during the transition from the normal to the inflamed state demonstrated that the first increase in background discharge took place 1-1.5 h after injection of carrageenan. 6. The proportion of noxious pressure units was reduced and that of moderate pressure units increased in inflamed muscle. In this case the difference was significant for group IV units only. 7. The response curves upon mechanical stimulation did not show significant differences in normal and inflamed muscle, i.e., sensitized noxious pressure units behaved similar to real touch units or moderate pressure units with respect to their mechanical excitability. 8. No apparent correlation existed between the receptors' mechanical threshold and degree of background activity in inflamed muscle. This suggests that the inflammation-induced change in mechanical excitability and development of background activity are independent phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neuronal activation at the spinal cord and medullary pain control centers after joint stimulation: a c-fos study in acute and chronic articular inflammation

Chronic inflammatory pain induces short- and long-term central changes, which have been mainly studied at the spinal cord level. Supraspinal pain control centers intrinsically connected with the dorsal horn are also prone to be affected by chronic inflammatory pain. C-fos expression was used as a neuronal activation marker at spinal and supraspinal levels to i) compare acute and chronic articular inflammation, and ii) analyze the effects of brief innocuous or noxious stimulation of a chronically inflamed joint. Acute articular inflammation was induced by an inflammatory soup with prostaglandin E(2) and bradykinin, both at 10(-5) M. Chronic articular inflammation consisted of 14 days of monoarthritis. Early c-fos expression was studied 4 min after inflammatory soup injection or stimulation of the arthritic joint whereas late c-fos expression was evaluated 2 h after those stimuli. At the spinal cord, the analysis was focused on the dorsal horn (laminae I-V) and supraspinally, five major regions of the endogenous pain control system were considered: the caudal ventrolateral medulla (VLM), the dorsal reticular nucleus (DRt), the ventral reticular nucleus (VRt), the nucleus of the solitary tract (Sol) and the rostroventromedial medulla (RVM). Acute articular inflammation induced early and late increases in c-fos expression at the spinal level and late increases supraspinally whereas the effects of monoarthritis were more moderate and restricted to the spinal cord. When monoarthritic animals were subjected to gentle touch or bending of the joint, early increases in c-fos expression were detected supraspinally, but not at the spinal level. In this region, noxious mechanical stimulation induced late increases in non-inflamed animals and both early and late increases in monoarthritic rats. Supraspinally, noxious stimulation induced only late increases in c-fos expression. The present results show complex differences in the patterns of c-fos expression between the spinal cord and medullary areas of the pain control system during articular inflammation, which indicate that the somatosensory system is differentially affected by the installation of chronic pain.     

Comparison of anterior cingulate and primary somatosensory neuronal responses to noxious laser-heat stimuli in conscious, behaving rats

In this study, we investigated single-unit responses of the primary sensorimotor cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the tail of the rat. The influences of morphine on these nociceptive responses were also compared. Multiple single-unit activities were recorded from two eight-channel microwire arrays chronically implanted in the tail region of the SmI and ACC, respectively. CO2 laser-heat irradiation of the middle part of the tail at an intensity slightly higher than that causing a maximal tail flick response was used as a specific noxious stimulus. Examined individually, ACC neurons were less responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC units (n = 125) responded compared with 88% of the SmI units (n = 74). Among these responsive ACC units, many had a very long latency and long-lasting excitatory type of response that was seldom found in the SmI. When ensemble activities were examined, laser heat evoked both short- (60 approximately 150 ms) and long-latency (151 approximately 600 ms) responses in the SmI and ACC. Latencies of both responses were longer in the ACC. Furthermore, a single dose of 2.5-10 mg/kg morphine intraperitoneally suppressed only the long latency response in the SmI, but significantly attenuated both responses in the ACC. These effects of morphine were completely blocked by prior treatment with the opiate receptor blocker, naloxone. These results provide further evidence suggesting that the SmI and ACC may play different roles in processing noxious information.