The isolated spinal cord-skin preparation of the newborn rat and effects of some algogenic and analgesic substances

We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were recorded extracellularly from the third lumbar ventral root. Application of capsaicin (0.5-2 μM) or KCl (60–350 mM) with brief pressure pulses to the perfusion bath of the skin evoked a depolarizing response of 20- to 40-s duration in the ventral root. The response was depressed by [Met⁵]enkcphalin (0.03–3 μM). morphine (0.1–2 μM) and a tachykinin antagonist, [D-Arg¹,D-Trp^7,9,Leu¹¹] substance P (spantide), 1–10 μM), applied to the spinal cord by superfusion, whereas the response was augmented by centrally administered calcitonin gene-related peptide (0.1–0.2 μM) or bicuculline (0.5–1 μM).     

辣椒素对慢性脊髓损伤大鼠排尿功能的影响

目的：明确辣椒素对正常大鼠和慢性脊髓损伤(SCI)大鼠排尿功能的影响和作用的可能机制。方法：建立SCI的动物模型，实验大鼠和正常大鼠分别全身给药或膀胱内灌注辣椒素，记录膀胱内压力变化图(CMG)和尿道外括约肌肌电图(EUS-EMG)的改变。结果：正常大鼠辣椒素全身用药后出现非排尿性膀胱收缩，排尿效率下降，但排尿压不受影响。膀胱内灌注辣椒素亦会导致排尿效率降低而不影响排尿压。SCI大鼠全身用药后非排尿性膀胱收缩消失，残余尿量减少，排尿压下降，但排尿效率提高，膀胱内用药则可完全阻断排尿反射。结论：对辣椒素敏感的膀胱感觉传入神经参与正常大鼠和SCI大鼠的排尿反射。对正常大鼠起稳定膀胱逼尿肌的作用，而对SCI大鼠则是引起膀胱灌注时非排尿性收缩的原因，因此，阻滞感觉传入神经纤维是治疗SCI后膀胱高反射的有效方法。     

Prostaglandins and CGRP release from cardiac sensory nerves

Summary (1) The possible influence of Prostaglandins (PG) E₁ and I₂ as well as ischaemia, ouabain and bradykinin on the outflow of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) from the guinea-pig heart was studied in vitro. (2) Exposure to PGE₁ (10^–5 M), but not PGI₂ (10^–5 M), induced an increased outflow, suggesting release of CGRP-LI. PGE₁ simultaneously increased the contractile force and heart rate while no effects were observed on perfusate volume or outflow of NPY-LI. PGI₂ had no effect on contractile parameters or coronary flow. In separate experiments on capsaicin-pretreated animals, the stimulatory effects of PGE₁ on heart rate and contractile force remained unchanged while no increased CGRP-LI outflow was detectable. (3) Ouabain, bradykinin and reperfusion after total stop-flow ischaemia was associated with an indomethacin-resistant increase in perfusate levels of CGRP-LI but not of NPY-LI. While ouabain markedly increased the contractile force, exposure to bradykinin or ischaemia did not induce any clear-cut changes in contractile force or heart rate. (4) Capsaicin-exposure evoked a markedly increased outflow of CGRP-LI but not of NPY-LI in combination with an increase in heart rate and a decrease in contractile force. Repeated administration of capsaicin induced tachyphylaxis. The stimulatory effects of capsaicin on CGRP-LI outflow and heart rate, but not the negative inotropic effect, did not occur in capsaicin-pretreated animals. (5) It is concluded that PGE₁, but not PGI₂, can activate cardiac capsaicin-sensitive fibres as revealed by increased outflow of CGRP-LI. The cardiostimulatory effects induced by PGE₁ are not related to CGRP release, however. A possible prostaglandin link in the CGRP-LI released by ouabain, bradykinin or ischaemia seems unlikely. Send offprint requests to: A. Franco-Cereceda at the above address     

Neuroplastic effects of neonatal capsaicin on barrel cortex of adult rat. An electrophysiological and autoradiographic study

Capsaicin (50 mg/kg s.c./25 μl) was administered to rats on the 2nd and 5th days after birth. The animals were raised, and from the age of 3 months the properties of the evoked activity were tested in the contralateral barrelfield. This neonatal capsaicin treatment was found to induce profound changes in the responsiveness of the barrel cortex in the adult rats: (1) the receptive field of the neurons in the Cl barrel was expanded; units within a particular barrel were driven by a significantly larger number of vibrissae than in the controls. (2) The rate of discharge evoked by the related vibrissa deflection was enhanced, while (3) the angular sensitivity of the neurons was decreased. (4) The most prominent change in cortical activity was observed by autoradiography: capsaicin-treated rats exhibited an enhanced labelling of different types of neurons throughout the hemisphere (surpassing the cortical representation of stimulated vibrissae). The present observations indicate that neonatal capsaicin affects the functional activity of the rat somatosensory cortex. It is suggested that unmyelinated sensory afferents play a role in the development of the rat somatosensory system.     

The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B

Eosinophilic bronchitis without asthma can cause a persistent non-productive cough which is resistant to bronchodilator therapy. To understand the mechanism of the cough in this disorder, an animal model of eosinophilic bronchitis was developed. Guinea-pigs were treated with transnasal administration of polymyxin B or saline twice a week for 3 weeks. The number of eosinophils in bronchoalveolar lavage fluid increased in polymyxin B-treated animals when compared with those treated with saline. In addition, histological examination showed that the number of eosinophils infiltrated into the tracheal epithelium increased; injury to the tracheal epithelium was greater in polymyxin B-treated animals. The numbers of coughs induced by saline and each concentration of capsaicin (10^–18, 10^–16, 10^–14M) were greater in the polymyxin B-treated animals. FK-224 (a neurokinin receptor antagonist) decreased the heightened cough reflex in this animal model of eosinophilic bronchitis. These findings suggest that neuropeptides, and particularly neurokinins, are involved in the heightened cough receptor sensitivity in eosinophilic bronchitis without asthma. This has implications for better understanding of this disorder and its treatment.     

Salivary cooling,escape reaction and heat pain in capsaicin-desensitized rats

Salivary thermolytic mechanism (weight of salivary glands, effect of desalivation on water intake and body temperature, grooming activity) as well as escape behaviour and reaction to heat pain were studied in capsaicin-desensitized and control rats exposed to various warm ambient temperatures. Body temperature of the desensitized rats increased more than the controls at all the ambient temperatures studied (32, 34 and 36°C); however, significant differences in the mechanism of salivary cooling were obtained only at 34 and 36°C. Central impairment of saliva spreading in desensitized rats seems evident. Complete surgical desalivation did not increase hyperthermia of control and desensitized animals in warm environments. Therefore other mechanisms, primarily vasodilatatory, must also be involved in the rat's thermolytic normal response. Although desensitized rats did not show a tendency to escape from the warm environment their response to heat pain was normal. In conclusion, it is suggested that heat perception in desensitized animals is impaired; however, the existence of some capsaicin-insensitive thermolytic mechanisms (prone extension of the body) cannot be excluded.Supported by the Scientific Research Council, Ministry of Health, Hungary /4-05-0303-04-2/0/ and MTA-OM-MÉM-EÜM 70.211/79     

Ambient temperature related sleep changes in rats neonatally treated with capsaicin

Ambient temperature related sleep changes in rats neonatally treated with capsaicin. PHYSIOL BEHAV 00(0) 000-000, 2004. The study was conducted on adult male Wistar rats, neonatally treated with capsaicin to destroy the peripheral warm receptors. The sleep-wakefulness was recorded for 5 h at an ambient temperature (T(amb)) of 18, 24, 30 and 33 degrees C on different days. The rectal temperatures (T(r)) of the rats were studied on exposure to 6 and 37 degrees C for 2 h to assess their thermoregulatory ability. The changes in the behavioral thermoregulation were assessed by noting the thermal preference of rats when they were placed in an environmental chamber with 3 interconnected compartments maintained at 24, 27 and 30 degrees C. Slow wave (SWS) and rapid eye movement (REM) sleep were decreased at 18 degrees C and increased at 30 degrees C, in control rats. There was a decrease in REM sleep and no change in SWS when T(amb) was raised from 30 to 33 degrees C. However, in neonatally capsaicin treated rats, sleep was increased even at 33 degrees C, though there was no significant change in sleep when T(amb) was increased from 18 to 24 degrees C. Capsaicin treated rats showed thermoregulatory deficiency at 37 degrees C but the thermal preference was unaltered in these rats. The results suggest that the central warm receptors can produce alteration in sleep at different T(amb), even in absence of peripheral warm receptors. The behavioral thermoregulation was unaffected in these rats, though their ability to defend the body temperature in warm environment was affected.     

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     

Reduced responsiveness of locus coeruleus neurons to cutaneous thermal stimuli in capsaicin-treated rats

Recent electrophysiological experiments have shown that brain norepinephrine (NE) neurons in the locus coeruleus (LC) are activated by cutaneous thermal stimuli of both non-noxious and noxious character. In the present study the LC neuronal response to thermal stimuli was used to evaluate cutaneous thermal sensitivity in capsaicin-treated rats, a treatment that is described to cause impaired thermoregulation. Capsaicin treatment, of neonates as well as of adult rats, caused a reduced responsiveness of brain LC neurons to thermal stimuli. The results suggest that a reduction in peripheral thermal afferent transmission may be one mechanism underlying the capsaicin-induced thermoregulatory dysfunction.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.