Subcutaneous Injection Of Capsaicin Research Articles

Importance of endogenous nitric oxide synthase in the rat hypothalamus and amygdala in mediating the response to capsaicin.

Although capsaicin has been shown to activate certain neuronal groups in the hypothalamus and amygdala, the neurotransmitters involved and the exact mechanism of action are not clearly understood at present. The aim of this study was to examine the hypothesis that the effect of capsaicin in the rat hypothalamus and amygdala primarily involves direct activation of the endogenous nitric oxide synthase (NOS) neurons responsible for the synthesis of nitric oxide (NO). Subcutaneous capsaicin injection in male rats, compared with vehicle, caused a significant increase in Fos expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and medial and cortical amygdala. The expression of nicotinamide adenine dinucleotide phosphate diaphorase, a histochemical marker for NOS, was also increased in these brain areas in addition to the periventricular and lateral hypothalamic area and central amygdaloid nucleus. Also, capsaicin significantly increased the expression of neuronal NOS messenger RNA and protein in the PVN, SON, and medial amygdala as demonstrated by in situ hybridization and immunohistochemistry, respectively. A higher proportion of the NOS neurons in the PVN, periventricular region, SON and amygdala showed Fos expression in response to capsaicin than vehicle injection. There was little, if any, Fos activation in the NOS-positive neurons in the lateral hypothalamic area. The capsaicin-induced activation of the hypothalamic PVN and SON neurons and the medial amygdaloid nucleus was attenuated in the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) -pretreated animals in comparison with the inactive enantiomer D-NAME. These observations indicate that activation of the endogenous NOS system and production of NO constitute a major pathway through which capsaicin exerts its effect within the hypothalamus and amygdala.

Somatotopic Activation of Opioid Systems by Target-Directed Expectations of Analgesia

We induced specific expectations of analgesia on four different parts of the body to understand how endogenous opioid systems are activated by expectancies. The left hand, right hand, left foot, and right foot were simultaneously stimulated by means of a subcutaneous injection of capsaicin, which produces a painful burning sensation. Specific expectations of analgesia were induced by applying a placebo cream on one of these body parts and by telling the subjects that it was a powerful local anesthetic. In such a way, expectancy of the anesthetic effect was directed only toward the part on which the placebo cream was applied. We found that a placebo analgesic response occurred only on the treated part, whereas no variation in pain sensitivity was found on the untreated parts. If the same experiment was performed after an intravenous infusion of the opioid antagonist naloxone, this highly spatial-specific placebo response was totally abolished, indicating that it was completely mediated by endogenous opioid systems. These findings show that a spatially directed expectation of pain reduction is capable of inducing a specific effect only on the part of the body which is the target of the expectation. Most important, this specific effect is mediated by endogenous opioids, indicating that placebo-activated opioids do not act on the entire body but only on the part where expectancy is directed. This suggests that a highly organized and somatotopic network of endogenous opioids links expectation, attention, and body schema.

A role for nitric oxide in the median eminence and arcuate nucleus response to capsaicin treatment in rats

This study examined a possible functional involvement of nitric oxide (NO) in the median eminence (ME) and arcuate nucleus (ARC) after capsaicin treatment in rats. Subcutaneous injection of capsaicin increased nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the ARC-ME compared with vehicle treatment. Fos expression was increased in the ARC after capsaicin injection compared with vehicle-treated rats. Pretreatment with the NO synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) attenuated the effect of capsaicin on Fos expression and NADPH-d reactivity in the ARC-ME in comparison with rats injected with D-NAME, the inactive stereoisomer of L-NAME. These observations suggest that NO makes a major contribution to the response of the ARC-ME to a stressor such as capsaicin.

Electron microscopic demonstration of nick end-labeled DNA fragments during capsaicin-induced apoptosis of trigeminal primary neurons in neonatal rats

DNA fragmentation was induced in the trigeminal ganglion of newborn rats by subcutaneous capsaicin injection (50 mg/kg). Twenty-four hours later, numerous roundish profiles were intensely labeled by both a DNA polymerase I-mediated nick translation method and a terminal transferase-mediated tailing method. Direct electron microscopic examination of labeled profiles indicated that the labeled profiles were neurons at earlier stages of apoptosis. DNA fragmentation signal was first detected in the nucleoplasm and later spread to the cytoplasm. The cell finally disintegrated forming many small apoptotic bodies. DNA fragmentation signal in the apoptotic bodies was readily labeled by the tailing but not the translation method.

Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism

To clarify the mechanism of capsaicin-induced primary neuronal cell death, newborn and adult rats were given a subcutaneous injection of capsaicin (50 mg/kg). Neonatal capsaicin injection induced neuronal apoptosis in the trigeminal ganglion. Apoptotic neurons had peripheral stacks of long parallel endoplasmic reticulum that are characteristic to primary neurons of the B-type, and exhibited nucleoplasmic condensation, nuclear shrinkage and cytoplasmic fragmentation. Light microscopically, apoptotic neurons exhibited a sign of DNA fragmentation as revealed by a nick end labelling method. The proportion of apoptotic cells was quite low during the first 12 h after capsaicin injection (<1%), rapidly increase to 10.44% by 24 h, and decreased to 0.29% by 48 h. Normal and vehicle control levels of apoptosis were <1%. Nerve growth factor (NGF, 0.5 mg/kg) simultaneously administered with capsaicin reduced the incidence of apoptosis by about 35% at 24 h post-injection. Neonatal transection of the infraorbital nerve induced neuronal apoptosis similar to that produced by the neonatal capsaicin in the maxillary division of the trigeminal ganglion. Unlike capsaicin, however, the neurotomy-induced apoptosis was seen in neurons of both the A- and B-types. Neither the capsaicin injection nor the neurotomy induced apoptosis in adult rats, though mitochondrial swelling similar to that seen at 0.5 h after neonatal capsaicin was observed after capsaicin injection in adults. The results indicate that the capsaicin-induced and nerve injury-induced primary neuronal damages in newborn rats share a common final pathway, apoptosis.

A novel method for detecting the analgesic effect of drugs by quantifying body movement after noxious stimulation in neonatal rat

We developed a method for quantifying nociceptive struggling in neonatal rats induced by bolus, subcutaneous injection of capsaicin (3–3000 ng). The response was quantified by using an audio speaker and electrical instruments such as an amplifier, a rectifier, and a monostable multivibrator. Using this method, we were able to quantify the nociceptive response which appeared immediately after injection of capsaicin. The response peaked at 0–1 min, and then decayed during next 1–3 min. Furthermore, this method also detected that the magnitude of the response increased dose-dependently up to the maximum dose of 3000 ng. In an experiment testing the suitability of this method for screening analgesics, it was shown that morphine (0.03–0.3 mg/kg, s.c.) inhibited the response dose-dependently with an ID 50 value of 0.089 mg/kg and that the analgesic effect of morphine (1 mg/kg, s.c.) was reversed by naloxone (0.03–0.1 mg/kg, s.c.). Thus it can be concluded that this method is useful to quantify the capsaicin-induced nociceptive response and is suitable for screening analgesics.

Analgesic effect of subcutaneous administration of oxygen-ozone. A blind study in the rat on the modulation of the capsaicin-induced edema.

The Authors have explored a new complementary approach, employed in the last 40 years for, among other uses, medical purposes: oxygen-ozone therapy. Anecdotal works have highlighted interesting results obtained in disk herniation with infiltration of paravertebral muscles with oxygen-ozone. To verify the existence of a nociceptive effect and investigate a possible mechanism of action, an experimental model of edema induction by subcutaneous capsaicin injection in the rat paw was employed. Oxygen-ozone, in different concentrations (10 microg/ml, 20 microg/ml and 30 microg/ml) has been injected both ipsi- and contralaterally to the paw 30 minutes before the administration of 50 microg capsaicin in 50 microl of physiological solution. Results show that the contralateral injection of the O2-O3 mixture modulates the edema response in the paw. Statistical significance, for the 20 microg/ml mixture, lasts as far as 45 minutes after administration of the capsaicin. No efficacy has been found for the 10 and 30 microg/ml concentrations. An injection of the same quantity of gas in the ipsilateral paw to the capsaicin-induced edema determines a worse edema than that observed in the control group, as if the ozone mixture added its irritative effect to that of capsaicin. It is interesting to note that the administration of oxygen alone cause a greater edema than the oxygen-ozone mixture.

Capsaicin-induced rapid receptive field reorganization in cuneate neurons.

1. To determine whether activity in unmyelinated or thinly myelinated primary afferents affects the organization of cutaneous receptive fields (RFs) in the cuneate nucleus, subcutaneous injections of capsaicin were made into the RFs of cuneate neurons in anesthetized cats. The effects of capsaicin injection on RF size and position, response properties, and spontaneous firing rates were determined during single-unit recordings. 2. Subcutaneous injection of capsaicin (10% dissolved in 70% ethanol) into peripheral RFs produced rapid RF reorganization in all neurons tested (n = 20), even when the original RF remained responsive to tactile stimulation. RF reorganization was marked by the appearance of newly responsive RFs. These RFs appeared as either contiguous expansions of the original RF or as new, noncontiguous fields. Control injections of the vehicle alone never produced RF reorganization (n = 9). RF reorganization was not related to changes in spontaneous activity. 3. Following capsaicin-induced RF reorganization, subcutaneous injections of lidocaine were made into the original RFs (n = 8). These injections produced no additional RF reorganization in seven of the eight neurons, even though in each case the lidocaine injections produced at least partial blocks of responsiveness from within the original RF. 4. In approximately one-half of the neurons (9 of 20), the reorganized RFs had response properties that were different from those of the original RF. This result suggests that, for neurons in the dorsal column nuclei (DCN), physiological mechanisms that normally mask inputs and restrict RF size can give rise to response specificity. 5. The results of these experiments demonstrate that capsaicin-induced RF reorganization, which has been reported previously in ventrobasal thalamus and primary somatosensory cortex, can arise within the dorsal column-medial lemniscal system, at the level of the DCN. The present results also provide evidence that rapid RF reorganization in cuneate neurons can be produced by blockade of a subset of peripheral afferents that are sensitive to capsaicin.

P-103 - Nociceptive response induced in newborn rats by subcutaneous injection of capsaicin.

P-103 - Nociceptive response induced in newborn rats by subcutaneous injection of capsaicin.

Modulation of rat chorda tympani nerve activity by lingual nerve stimulation.

1. A subpopulation of lingual nerve (LN) fibers surround and/or terminate in taste buds in fungiform papillae. One possible function of these fibers is to modulate chorda tympani fiber (CT) or taste responses. To test this hypothesis, the rat LN was stimulated electrically at various voltages (to 20 V), and single- and multiunit CT responses to water-0.1 M NaCl cycles were recorded before, during, and after LN stimulation. 2. When a thermally controlled water-0.1 M NaCl stimulus cycle was applied onto the tongue's surface, the surface temperature remained constant, independent of the stimulation voltage. In the absence of a liquid stimulus, the tongue's surface temperature increased approximately 4 degrees C upon LN stimulation for voltages > or = 5 V. This temperature increase, caused by vasodilation by way of the axon reflex flare mechanism, was taken as evidence that LN stimulation induces peptide release. 3. Comparison of CT activity before LN stimulation with the activity either during or after stimulation revealed statistically significant changes in CT activity. During LN stimulation the CT activity decreased. After LN stimulation, the variability in amount of CT activity increased. 4. In rats treated postnatally with subcutaneous injections of capsaicin to reduce or eliminate polymodal nociceptors, LN stimulation did not produce increases in the tongue's surface temperature or changes in CT activity. 5. Changes in CT activity could be detected seconds after LN stimulation, suggesting that the intragemmal and/or perigemmal LN fibers modulate CT activity. 6. The physiological implications of this study suggest that CT responses to salt can be modulated by endogenous compounds (probably peptides), eating foods that activate LN responses (e.g., foods that are very acidic or contain capsaicin) may modulate taste responses, and peri- and intragemmal fibers should be considered an integral part of the taste receptor system.

Early morphological changes of primary afferent neurons and their processes in newborn mice after treatment with capsaicin.

Degenerating figures of dorsal root ganglion (DRG) neurons and their central and peripheral processes (dorsal root and saphenous nerve) and terminals (central terminals in the superficial dorsal horn and cutaneous nerve of the hind paw dorsal skin) of neonatal mice were examined 30 min, 1, 2 and 5 h, and 2, 3, 5, and 10 days after subcutaneous injection of capsaicin on post-natal day 2. Many small DRG neurons showed degeneration 1 h after treatment. Scarcely any features of degeneration were seen in the DRG and dorsal root 10 days after treatment. The degenerating aspects of terminal axons in the marginal layer of the superficial dorsal horn were characterized by enlarged round axons with closely packed osmiophilic materials, lamellar bodies, and loss of axoplasmic organelles. Two types of central terminals (C-terminals) showed degeneration in the substantia gelatinosa from 30 min after treatment onward. One type consisted of small, round, sinuous or slender dark terminals (CI-terminals), and the other of large, pale, round or angular terminals (CII-terminals). Those that degenerated markedly had homogeneously electron-dense axoplasm with dilated synaptic vesicles and inclusion bodies. Extensive degeneration of terminal axons in the marginal layer occurred 5 h after treatment, whereas conspicuous degeneration of C-terminals occurred from 30 min to 10 days after treatment in the substantia gelatinosa. CI-terminals showed marked degeneration during the first 3 days, whereas marked degeneration of CII-terminals occurred between 5 and 10 days after treatment. This time difference between the peaks of degeneration of CI- and CII-terminals indicates an important difference in the origins of these two types of capsaicin-sensitive, nociceptive fibers in the superficial dorsal horn; CI-terminals are derived from small DRG cells, whereas CII-terminals are derived from larger DRG cells. Unmyelinated axons in the dorsal root, saphenous nerve, and dorsal skin of the hind paw showed similar degeneration patterns 2 h after treatment to those of terminal axons in the marginal layer. Thus, the degenerating profiles in the marginal layer suggest that these axons arose from collaterals of unmyelinated primary axons descending or ascending within the marginal layer. Numerous enlarged degenerating axons showing vacuolation were conspicuous in the dorsal skin 3 days after treatment. The synchronous degeneration of the smaller DRG neurons, their central and peripheral processes, and their CI-terminals in the substantia gelatinosa supports the idea that the smaller DRG neurons are directly influenced by capsaicin, and that their degeneration is followed by centrifugal degeneration.

Somatotopic and laminar organization of fos‐like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat

The distribution of fos-like-immunoreactivity (fos-LI) in the medullary and upper cervical dorsal horn was examined following noxious facial stimulation, in order to evaluate the use of fos as a marker for neuronal activation in trigeminal nociceptive pathways. Control animals that received urethane anesthesia and no facial stimulation showed substantial bilateral labeling in the trigeminal complex that was restricted to one rostrocaudal level, at the transition between the medullary dorsal horn (nucleus caudalis) and nucleus interpolaris. Noxious mechanical stimulation (pinch) of different facial sites produced labeling in the ipsilateral dorsal horn whose distribution varied predictably with the rostrocaudal and dorsoventral position of the facial stimulation site, such that rostral facial sites were represented rostrally in the dorsal horn and dorsal sites were represented ventrolaterally. The cornea was exceptional among the facial stimulation sites in that it had a specific representation at two distinct rostrocaudal levels, in C1 and the interpolaris-caudalis transition region; the position of the rostral peak was somatotopically inappropriate, based on the representation of other facial sites. The proportion of labelling in laminae III-IV relative to laminae I-II was higher with noxious mechanical stimulation than with noxious thermal (55 degrees C) or chemical (subcutaneous injection of capsaicin) stimulation. The proportion of labelling in laminae III-IV produced by electrical stimulation of the infraorbital nerve was no greater than that produced by pinch. The results suggest that fos-LI mapping can be a useful method for the investigation of somatotopy but is subject to serious limitations when used for the investigation of laminar organization. The results also suggest that the interpolaris-caudalis transition region may have properties that are distinct from those of the rest of the trigeminal complex, possibly related to an involvement in autonomic function.

Ultrastructural Study of Rabbit Lung Tissue Subsequent to Capsaicin Treatment over Several Days

The neurogenic basis of nonspecific airway hyperresponsiveness (NAH) is poorly understood. Under experimental conditions isocyanates can elicit bronchial hyperresponsiveness in animals. The purpose of our study was to determine whether reactions of neurosecretory granules in nonmedullated C fibers might play a role in NAH. Our experiments were based on the fact that capsaicin treatment causes depletion of neurosecretory granules in vicinity of C fibers. We gave rabbits repeated subcutaneous injections of capsaicin. The animals were then treated with toluene diisocyanate (TDI), inducing airway hyperresponsiveness upon acetylcholine (ACH) inhalation. In capsaicin-treated animals the neurosecretory granules were not evident ultrastructurally and airway hyperresponsiveness did not occur in response to TDI treatment. Controls that were not treated with capsaicin displayed both neurosecretory granules ultrastructurally as well as airway hyperresponsiveness to ACH. We conclude that in the rabbit, NAH is related to the presence of neurosecretory granules adjacent to nonmedullated C fibers.

The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord

A capsaicin test involving peripheral nociception, which produces behaviour similar to that elicited by formalin, is described in mice. Capsaicin was injected subcutaneously (s.c.) into the dorsal surface of a hindpaw and the time the animals spent licking the paw was recorded. Doses of capsaicin of 6.25–1600 ng induced nociception, during a period of 5 min, starting immediately after injection and disappearing completely at 10 min. Intrathecally (i.t.) administered [ d-Arg 1, d-Trp 7,9, Leu 11]substance P (spantide), a tachykinin antagonist and [ d-Phe 7, d-His 9]substance P (6–11), a selective antagonist of substance P (SP), inhibited the capsaicin-induced behaviour, in a dose-dependent manner. This licking behaviour was also inhibited by intrathecal administration of SP antiserum but not by somatostatin (SOM) antiserum. Intrathecal pretreatment with capsaicin resulted in a marked reduction of the licking response, following subcutaneous injection of capsaicin into the paw. Capsaicin-induced licking was not affected by intrathecal administration of cyclo[7-aminoheptanoyl-Phe- d-Trp-Lys-(OBz)-Thr], a SOM antagonist and by intrathecal pretreatment with cysteamine, a SOM depletor. This nociceptive test may allow discrimination between SP- and SOM-mediated responses in the spinal cord of the mouse.

Effect of capsaicin on nasal secretion in anesthetized ferrets

In urethan-anesthetized ferrets, we investigated the nasal response to capsaicin infused via a catheter inserted retrogradely into the lingual artery. Capsaicin dose-dependently increased fluid output from the nose (nasal fluid output) and the lateral nasal gland (glandular fluid output). The secretory response to capsaicin (80 nmol/kg ia) was completely blocked by atropine and hexamethonium, indicating that a cholinergic reflex mediates capsaicin-induced nasal hypersecretion in this model. The amount of nasal secretions collected as nasal fluid output was similar to that collected as glandular fluid output, indicating that the lateral nasal gland contributes significantly to this increase in nasal secretions induced by intra-arterially administered capsaicin. In addition, the nasal fluid output had a higher protein concentration and osmolality than the glandular fluid output. This finding suggests that the gland is not the sole site of action of capsaicin on the nasal secretory response. It is likely that capsaicin also increases microvascular permeability, thereby contributing further to the alteration in the nasal secretions. Finally, repeated subcutaneous injections of capsaicin significantly reduced the secretory response to capsaicin, indicating the development of desensitization in vivo. These results support the role of capsaicin-sensitive sensory nerves in mediating a secretory response in the ferret nose.

Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress.

The effect of intracerebroventricular injection of the mitosis inhibitor colchicine and of immobilization stress, subcutaneous injection of capsaicin, and intraperitoneal injection of hypertonic salt solution on expression of c-Fos-like immunoreactivity was studied in the rat brain with immunohistochemistry. All the procedures induced c-Fos immunoreactivity in parvocellular neurons of the paraventricular nucleus, and many of these neurons also contained corticotropin-releasing factor immunoreactivity. c-Fos immunoreactivity was also observed, for example, in subpopulations of neurons in the locus coeruleus, the ventrolateral medulla oblongata, and the nucleus tractus solitarii. Many of these cells also expressed catecholamine-synthesizing enzymes. The results suggest that intraventricular injection of colchicine is a stressful stimulus and support the view that several catecholamine cell groups in the lower brainstem are part of the brain circuitry mediating stress reactions, as are the hypothalamic neurons that contain corticotropin-releasing factor.

Regionally selective elimination of cutaneous thermal nociception in rats by neonatal capsaicin

We have studied thermal and mechanical nociception in anesthetized adult rats that had received subcutaneous injections of capsaicin as neonates. This treatment appeared not to have impaired mechanonociception in any of the body regions that were examined. In contrast, thermal nociception was present in some locations and absent in others. Its total disappearance from back skin correlated with the loss of C fiber responsiveness in the dorsal cutaneous nerves (DCNs); electrical excitation of these nerves now failed to evoke the delayed component of the cutaneus trunci muscle reflex, although the early reflex response, elicited by excitation of the mechanosensitive A delta axons, was unaffected. Heat nociception was similarly eliminated from the nonpad glabrous skin of the paws. When the stimulus was applied selectively to the pads, however, a normal foot-withdrawal response was evoked. The probable basis of this differential heat responsiveness in the paws was revealed by the use of the Evans Blue technique in untreated animals; antidromic activation of the paw nerves to excite their C fiber population led to dye extravasation in the glabrous skin around the pads but to almost none in the pads themselves, indicating a relative absence in the pads of a nociceptive C fiber innervation. In capsaicin-treated animals, the tail-flick test revealed a significantly reduced responsiveness to noxious heat in the tail. These results may explain some of the anomalies among the reports of the effects of neonatal capsaicin. It appears that in strategically exposed locations exemplified by the paw pads and tail, capsaicin-resistant axons that could be the relatively fast-conducting A delta ones are involved in the signalling of noxious heat.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of capsaicin upon afferent and efferent mechanisms of nociception and temperature regulation in birds

(1) Acute capsaicin effects on nociception in the conscious chicken were tested by close arterial injection. The threshold dose to elicit nocifensive and autonomic responses was 50 micrograms, i.e., two to three orders of magnitude higher than in mammals but four times lower than in pigeons. (2) Foot withdrawal from hot water remained unchanged after capsaicin was injected either intravenously in the chicken at a cumulative dose of 600 mg/kg or perineurally at a dose of 100 micrograms into the sciatic nerve of pigeons. (3) Temperature regulation and body temperature in the chicken were not affected by subcutaneous injection of capsaicin, but intravenous infusion at rates of 2-5 or 10-13 mg X min-1 X kg-1 transiently lowered body temperature by 1.5 degrees C and stimulated panting and sometimes vasodilatation of the comb. Repeated capsaicin infusion produced temporary tachyphylaxia but no permanent desensitization. (4) A cumulative dose of 1 g/kg body weight capsaicin reduced the relationship between breathing frequency and respiratory evaporative heat loss in the duck. This deficit was compensated by more pronounced panting and, thus, did not indicate any impairment of temperature regulation. (5) Injection of capsaicin into the sciatic nerve depleted substance P in the dorsal horn of rats. Similar treatment in pigeons caused an increase of substance P immunoreactivity in the dorsal horn. (6) The effects of high capsaicin doses in birds indicate only low susceptibility of afferent neural mechanisms. Some of the effects may be due to a capsaicin action upon efferent neural mechanisms.

Loss of spinothalamic tract neurons following neonatal treatment of rats with the neurotoxin capsaicin.

The purpose of the present experiments was to determine whether the organization of spinothalamic tract (STT) cells of adult rats was altered following the loss of most of their small-diameter peripheral afferent fibers, resulting from the neonatal administration of capsaicin. Rat pups were randomly assigned to serve as normal controls, to serve as vehicle controls, or to receive subcutaneous injections of capsaicin (50 mg/kg) on postnatal day (PND) 1, 2, 7, or 15; or an injection on PND 1, 3, and 5. When 60 days old, they were anesthetized and received 0.1-microliter thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) in the area of the central lateral nucleus (CL), the posterior group (PO), and the ventrobasal complex (VB), or the area of CL or VB. Following a survival time of 48 hr, the animals were perfused, and neuronal HRP reaction product was visualized with tetramethylbenzidine. The number and distribution of WGA:HRP-labeled STT neurons varied in treated animals with the time of capsaicin injection. Rats injected with capsaicin on or before PND 7 demonstrated a significant reduction of labeled STT neurons from the superficial laminae of the spinal cord. Additionally, lamina I neurons were unlabeled in animals treated before PND 7 even with large thalamic injections. Differences in the distribution of labeled STT neurons could not be demonstrated for animals injected with capsaicin on PND 7 or PND 15, though there was a decrement in the number of labeled neurons in PND 7 animals. In order to make certain that absence of labeled STT neurons was not due to some technical error or to insufficient spread of WGA:HRP at the site of injection, six injections of WGA:HRP were placed in the thalamus of PND 1 and normal adult animals. Where the dense core of reaction product did not extend caudal to the posterior commissure, WGA:HRP-positive neurons were located and distributed similarly to those cases described for large thalamic injections. Neurons in superficial laminae of the nucleus proprius and lamina I of the contralateral spinal cord were labeled where the dense core of the thalamic injection extended into the mesencephalon of PND 1 animals. These studies indicate that the number and distribution of the cells of origin of the STT are altered in adult rats following their neonatal treatment with the neurotoxin capsaicin, and that this effect is limited to a critical postnatal period.

The effect of ambient temperature on rectal temperature, food intake and short term body weight in the capsaicin desensitized rat

1. Subcutaneous injections of capsaicin (mean cumulative dose: 80.1 +/- 3.6 mg , kg-1) permanently reduced the capacity of rats to withstand a hot environment when deprived of water. With water available, hyperthermia was discrete or absent in capsaicinized rats in hot environment. 2. Desensitization was followed by a significant decrease in both food intake and body weight. Treated rats recovered normal body weight after 3 weeks. 3. In a hot environment, compared to controls, food intake was significantly increased in capsaicin desensitized rats which maintained their body weight. In cold environment, food intake was decreased in capsaicin desensitized rats which lost body weight. At normal ambient temperature, food intake and body weight were similar in the 2 groups. 4. Caloric intake adjustment at high and at low temperatures was therefore disturbed in capsaicin desensitized rats. It is concluded that hypothalamic thermodetectors implicated in both thermoregulation and food intake behaviour could be partially damaged by capsaicin.