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Biomedical subjects

J L Henry

Publications and source records attributed to J L Henry.

At least 55 records · Page 3Linked to original sources
PubMed1995

mu-, delta- and kappa-opiate receptors mediate antinociception in the rat tail flick test following noxious thermal stimulation of one hindpaw.

Experiments were performed to investigate the possible involvement of spinal mu-, delta- and kappa-opiate receptors in mediating the antinociceptive effects of noxious thermal stimulation of one hindpaw on the tail flick reflex in the rat. Male Sprague-Dawley rats were implanted with chronic intrathecal catheters to the lumbar level of the spinal cord. After 5 to 7 days, they were lightly anesthetized with an i.p. injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). After baseline readings were taken in the tail flick test a conditioning noxious thermal stimulus, which consisted of immersion of one hindpaw in water at 55 degrees C for 90 sec, was applied and the effects on the latency of the tail withdrawal reflex were studied over the next 30 min. In animals pretreated with CSF intrathecally 10 min before the stimulus, an increase in tail flick reaction time was observed peaking at 30 sec after the stimulus. This response was attenuated in a dose-related manner by preadministration of the specific mu-opiate receptor antagonist, beta-funaltrexamine, the specific delta-opiate receptor antagonist, H-Tyr-Tic psi[CH2NH]-Phé-Phe-OH or the specific kappa-opiate receptor antagonist, nor-binaltorphimine. The data show that the antinociceptive effect on the tail withdrawal reflex from a brief noxious thermal stimulus is provoked heterosegmentally by the noxious conditioning stimulus to the hindpaw and is mediated by the endogenous release of ligands that bind to mu-, delta- and kappa-opiate receptors in the spinal cord.

Analgesics↗
PubMed1994

Noxious stimulation decreases substance P binding in rat spinal dorsal horn: competition by endogenous ligand?

To determine the participation of NK-1 receptors in mediating inputs from noxious thermal stimulation, sustained noxious stimulation was applied to anaesthetized rats by immersing one hind paw in water for 1.5 min at different temperatures. After sacrificing the animal, lumbar spinal cords were removed and 20 microns sections were incubated with [125I]BH-substance P. Compared with unstimulated controls, binding was the least in rats given a 55 degrees C stimulus and sacrificed 1 min after the stimulus; the greatest reduction was found in the superficial dorsal horn. Rats sacrificed at 10 min showed intermediate binding levels. Groups given less intense stimuli showed smaller decreases in binding. It is suggested that the decrease in binding was due to occupation of receptors by endogenous ligand, which is consistent with the idea that noxious stimulation evokes the release of substance P at the spinal level.

Animals↗
PubMed1994

Substance P released endogenously by high-intensity sensory stimulation potentiates purinergic inhibition of nociceptive dorsal horn neurons induced by peripheral vibration.

To investigate the interaction at the spinal level of endogenously released substance P with the effects of endogenously released adenosine, extracellular single-unit activity was recorded from dorsal horn neurons in the anesthetized cat. Vibration to the skin inhibited on-going activity of nociceptive neurons; 20 mg/kg caffeine reversibly blocked this inhibition, indicating mediation via adenosine receptors. In half of the cases, this inhibition was potentiated by iontophoretic application of substance P. High-intensity electrical stimulation to a sensory nerve produced excitation which was blocked by an NK-1 (substance P) receptor antagonist, implicating an endogenous neurokinin. When electrical stimulation preceded the vibrational stimulus, the inhibitory effect of vibration was potentiated. Thus, we suggest that endogenous substance P may potentiate the inhibitory response to endogenous adenosine. The results have important implications for integration of inputs from different sensory modalities, especially as they relate to nociception and pain.

Animals↗
PubMed1994

Specific contribution of lumbar spinal mechanisms to persistent nociceptive responses in the formalin test.

To determine whether a lumbar spinal mechanism mediates the late phase of the nociceptive response in the formalin test, we compared the effects of intrathecal (i.t.) lidocaine given pre- or post-formalin at the lumbar or thoracic level. Pre- but not post-formalin administration of lidocaine to the lumbar level significantly attenuated late phase nociceptive responses. In contrast, neither pre- nor post-formalin administration of lidocaine to the mid-thoracic level altered nociceptive responses. In rats chronically spinalized at the mid-thoracic level, nociceptive responses to formalin were observed which were blocked by i.t. pre-treatment with lidocaine at the lumbar level. These results suggest that a specific lumbar spinal mechanism is involved in the initiation of persistent nociception in the formalin test.

Anesthesia, Spinal↗
PubMed1994

Prolonged GABAA-mediated inhibition following single hair afferent input to single spinal dorsal horn neurones in cats.

To study the central processing mechanisms of sensory input from low threshold afferents to the spinal cord, we examined the excitatory response of single lumbar dorsal horn neurones to stimulation of hairs in the receptive field using a mechanically driven probe, and to activation of single hair follicle afferents using an intracellular current pulse to the cell bodies in the dorsal root ganglion. Experiments were done on anaesthetized, paralysed cats, spinalized at the L1 lumbar level. Responses of spinal neurones to two types of hair afferent input were characteristically different. The excitatory response to input from a single group II hair afferent (A beta; innervating guard hair follicle receptors) was multimodal, characterized by a small early depolarization followed by a sharp, large component with a slow, prolonged decay phase, whereas the response to input from a single group III hair afferent (A delta; innervating down hair follicle receptors) was unimodal. The unitary EPSPs in response to activation of group III hair afferents had a slower rise time and longer decay time constant than those in response to activation of group II hair afferents. When the receptive field of the afferent was located in the centre of the receptive field of the dorsal horn neurone, the gain of the central response was greater for the input from a single group II afferent (> 1) than that for the input from a single group III afferent (< 1). In the case of single group II hair afferents, when pairs of single action potentials or pairs of trains of action potentials were generated at intervals of 20 ms to 3 s, the response in the dorsal horn neurone to the second volley was markedly depressed at intervals of less than 2 s, without any apparent inhibition of the on-going rate of firing. The response to the second volley in single group III afferents was less depressed. This inhibition of the response to the second of a paired volley in single group II hair afferents was attenuated by administration of bicuculline, but not strychnine or naloxone. This indicates that the inhibition involves a GABAA-receptor-mediated mechanism. Bicuculline did not affect the late component of the response to single group II hair afferent input, but unmasked a late component of the response to mechanical stimulation of hairs.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1993

High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2.

The erbB-2 (or HER-2 or neu) gene is amplified and overexpressed in approximately one-third of cancers of the breast, stomach, and ovary. Evidence is accumulating that erbB-2 overexpression is associated with decreased survival of breast cancer patients. In an effort to understand how erbB-2 overexpression might impart a more malignant potential to breast cancer cells, we have searched for evidence of changes in gene expression associated with erbB-2 overexpression. Using differential screening of a complementary DNA library we identified several complementary DNAs that represent mRNAs the expression of which may vary according to erbB-2 level. One complementary DNA was studied in detail. The mRNA encoding the ribosomal protein L19 (1.9 kilobases) was more abundant in breast cancer samples that express high levels of erbB-2 (P < 6 x 10(-7)). The level of L19 mRNA expression varied over a 1- to 64-fold range among the tumor samples. No evidence of gene amplification for L19 was identified. The L19 overexpression in these breast tumor samples was not associated with the increased expression of the mRNAs for other ribosomal proteins (S16 and L26).

Amino Acid Sequence↗
PubMed1993

Neural mediation of the cardiovascular responses to intrathecal administration of substance P in the rat: slowing of the cardioacceleration by an adrenal opioid factor.

Substance P, given intrathecally at the second (T2) or ninth (T9) thoracic level in the anesthetized rat, increased heart rate, arterial pressure and circulating catecholamines. At T9 in adrenalectomized animals and at T2 in intact animals, the cardioacceleration was more abrupt than in intact animals injected at T9 suggesting that the adrenals are not necessary for the cardiovascular responses and that the adrenals may have released a factor which slows the neurally mediated cardioacceleration. As opioids are co-released with catecholamines from the adrenals, naloxone (10 mg/kg i.v.) or nalorphine HCl (which does not cross the blood-brain barrier; 10 mg/kg s.c.) was given 5 min before administration of substance P at T9 in intact rats. In both groups the cardioacceleration was similar to that elicited in adrenalectomized animals, indicating that the adrenal factor was opioid and that its action was peripheral rather than central. When propranolol (10 mg/kg i.v.) was given 3 or 15 min before, substance P increased arterial pressure but heart rate was unchanged, indicating that the opioid factor was not slowing the cardioacceleration by a direct effect on the heart. The results indicate that intrathecal administration of substance P produces a neurally mediated increase in arterial pressure and heart rate and induces the release of an adrenal opioid factor which slows the neurally-mediated cardioacceleration by an action in the periphery. This indicates a functional interaction between humoral and neural sympathetic mechanisms regulating the cardiovascular system.

Adrenal Glands↗
PubMed1993

Excitatory amino acid receptor mediation of sensory inputs to functionally identified dorsal horn neurons in cat spinal cord.

As excitatory amino acid receptors have been implicated in nociceptive sensory transmission, the principal objective of the present study was to investigate the effects of various excitatory amino acid antagonists on naturally evoked responses in spinal dorsal horn neurons. Extracellular single unit activity was recorded from functionally identified, spinal dorsal horn neurons in unanesthetized, decerebrated cats and in alpha-chloralose-anesthetized cats. The tests included iontophoretic application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV), the non-N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and kynurenate, and also the intravenous administration of the N-methyl-D-aspartate receptor antagonist, ketamine. In addition, attempts were made to determine the effects on these neurons of iontophoretic application of the excitatory amino acid agonists, L-glutamate, N-methyl-D-aspartate, quisqualate, (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and domoate. Marked differences were noted in the actions of agonists and antagonists between the responses observed in the unanesthetized, decerebrated and the anesthetized animals. In decerebrated cats, responses to hair afferent stimulation were blocked by kynurenate, 6-cyano-7-nitroquinoxaline-2,3-dione and 2-amino-5-phosphonovaleric acid. Responses to noxious thermal stimulation were attenuated by 2-amino-5-phosphonovaleric acid and in one unit also by ketamine. Neither 6-cyano-7-nitroquinoxaline-2,3-dione nor kynurenate affected the responses to noxious thermal stimulation. The proportion of cells responding to the agonists were: N-methyl-D-aspartate 24/27 (89%), quisqualate 12/13 (92%) and domoate 6/7 (86%). In chloralose-anesthetized cats, responses to hair afferent stimulation were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione and kynurenate but not by 2-amino-5-phosphonovaleric acid. Responses to noxious thermal stimulation were not affected by any of these antagonists, while the response to non-noxious thermal stimulation was blocked by 2-amino-5-phosphonovaleric acid, ketamine and kynurenate in the one neuron studied. The proportion of cells excited by the agonists differed from those observed in decerebrated cats: N-methyl-D-aspartate 9/32 (28%), quisqualate 50/54 (93%), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate 19/23 (83%) and domoate 17/38 (45%). Application of the putative endogenous excitatory amino acid precursor N-acetyl-aspartyl-glutamate (NAAG) did not elicit a response in any of the neurons studied.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

CP-96,345, but not its stereoisomer, CP-96,344, blocks the nociceptive responses to intrathecally administered substance P and to noxious thermal and chemical stimuli in the rat.

The effects of subcutaneous administration of the non-peptide NK-1 (substance P) receptor antagonist, CP-96,345, and its stereoisomer, CP-96,344, were tested in three nociceptive paradigms in the rat. In the first paradigm, tail flick responses were monitored before and after intrathecal administration of substance P (6.5 nmol) in rats pretreated subcutaneously with saline, CP-96,344 (5 mg/kg) or CP-96,345 (5 mg/kg). In the control groups, pretreated with saline (n = 6) or with CP-96,344 (n = 5), substance P reduced the tail flick reaction time at 1 min after administration to 38.3 +/- 5.1 (mean +/- S.E.M.) and 32.1 +/- 7.7% of the mean baseline value, respectively. In contrast, in the group pretreated with CP-96,345 (n = 6) the reaction time following administration of substance P was 98.8 +/- 3.3% of the baseline reaction time; this value was not significantly different from the baseline value of this group, indicating a block (P < 0.01) of the substance P-induced facilitation of the tail flick response. In the second paradigm, rats were anesthetized with a mixture of chloral hydrate (120 mg/kg, i.p.) and sodium pentobarbital (20 mg/kg, i.p.), and the effects were determined on tail flick reaction time of a sustained noxious cutaneous stimulation, immersing the tip of the tail in hot water at 55 degrees C. In the groups of rats pretreated with saline (n = 4) or with CP-96,344 (n = 7), this noxious stimulus produced a transient decrease in reaction time to 62-74% of the baseline value.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

L-NAME blocks responses to NMDA, substance P and noxious cutaneous stimuli in cat dorsal horn.

The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), administered i.v. (50 mg kg-1) or by iontophoresis, was tested on the responses of spinal dorsal horn neurones in cats anaesthetized with alpha-chloralose and spinally transected at the L1 level. Extracellular, single-unit recordings were obtained from functionally identified dorsal horn cells. All units included in this study were wide dynamic range neurones. L-NAME significantly reduced the responses of (i) twelve neurones to noxious thermal stimulation of the receptive field, (ii) nine neurones to noxious pinch, (iii) nine neurones to iontophoretic application of N-methyl-D-aspartate (NMDA) and (iv) ten neurones to iontophoretic application of substance P. The inhibition usually lasted for 50-70 min following i.v. administration and for 5-8 min after iontophoretic application of L-NAME. The responses of four neurones to iontophoretic application of quisqualate were not affected by L-NAME. The results suggest the possible involvement of nitric oxide in the mediation of the spinal effects of NMDA and substance P, and in the transmission of thermal and mechanical nociceptive imputs.

Animals↗
PubMed1993

Substance P and inflammatory pain: potential of substance P antagonists as analgesics.

Substance P has been implicated in peripheral inflammatory responses and recent evidence from animal models indicates that substance P (NK-1 receptor) antagonists are effective in blocking peripheral inflammatory responses as well as nociception (pain) associated with inflammation. Evidence implicating substance P in nociception is reviewed in this survey, along with evidence on the effects of NK-1 receptor antagonists and with some comments on the usefulness of such antagonists as analgesics.

Animals↗