Effects of capsaicin on receptive fields and on inhibitions in rat spinal cord.
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Biomedical subjects
Publications and source records attributed to M Fitzgerald.
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Capsaicin, a neurotoxin which acts specifically on sensory primary afferent C-fibres was applied locally to one sciatic nerve of a group of rats. One to sixteen days following this a series of behavioural and electrophysiological studies were performed. The latency of foot withdrawal of the rats to a controlled thermal noxious stimuli was significantly elevated (200%). The peak increase occurred on day 1 after treatment; the response then fell to a steady but elevated level for up to 16 days. Responses to noxious mechanical stimuli were unaffected by capsaicin treatment. Single unit analysis of the dorsal horn of the spinal cord showed that the number of neurones in deep laminae (4, 5 and 6) responding to a C peripheral volley was normal (60%) for the first 2 days after treatment. On day 3 post treatment, the number of cells with a C input began to fall reaching a maximal decrease on day 7 (25%), where it remained up to day 16. In contrast to this delayed effect on C-evoked responses, the number of cells responding to noxious heating of the skin fell from control levels of 60% down to 20% on day 1 and remained decreased for up to 16 days. The onset of thermal analgesia following local, capsaicin treatment, therefore, closely parallels the time course of the decrease of noxious heat-evoked responses in the dorsal horn. Since at early pretreatment times, the electrically C-evoked activity is normal these effects are likely to be due to action on peripheral C-fibre nociceptors in the skin. At a later stage capsaicin also appears to act on the central terminals of fibres reducing transmission to second order dorsal horn neurones.
The healing capacity of mechanically exposed and bacterially contaminated dental pulps was assessed in monkeys after capping with 2 commercial Ca(OH)2 containing compounds. One hundred eighty teeth in 7 monkeys were employed, 45 as untreated controls and 135 as treated exposures. Class V buccal cavity preparations resulting in pulpal exposure were prepared, left open to the oral cavity for 0, 1, 24 h or 7 days and employed as controls, or debrided, capped, restored with amalgam and left undisturbed for 5 weeks as treated exposures. Zero and 1 h untreated exposures presented damage from the mechanical trauma only, whereas 24 h and 7 day pulp wounds exhibited pronounced infiltrations of polymorphonuclear and mononuclear leukocytes. In addition, the 7 day exposures demonstrated several teeth with partial and total necrosis. Treated 0, 1 and 24 h exposures demonstrated wound healing, minimal pulp tissue inflammation, reorganization of soft tissue and formation of new hard tissue at the exposure site in 86 of 99 teeth. Treated 7 day exposures healed less frequently, showing signs of dentin bridging in 15 of 27 teeth. This study indicated that mechanically exposed and orally contaminated dental pulps in monkeys have a high capacity to resolve inflammation and initiate healing with new dentin formation at the exposure site when treated as described.
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The effect of systemic morphine (5 mg/kg) on the C-fibre evoked activity in the dorsal horn of decerebrate spinalized rats has been investigated. Activity in units recorded from lamina 5 was inhibited in a naloxone-reversible fashion by morphine. However, morphine produced variable changes in the C-evoked activity of units recorded within the substantia gelatinosa, some units showing excitation, some inhibition and some an alteration in the timing and pattern of the C-evoked activity.
Preliminary evidence has indicated that the number of nuclear bodies in uterine luminal epithelial cells of the immature rat may be related to the duration of nuclear retention of the estrogen receptor complex (Clark et al., 1978). To test this hypothesis, an ultrastructural analysis of nuclear and cytoplasmic differentiation was performed at 4, 12, 24, 48, and 72 hr after a single injection of estradiol or nafoxidine (synthetic estrogen agonist/antagonist) into 21 day female rats. Variations in nuclear and cytoplasmic differentiation and in the frequency of occurrence of nuclear bodies (simple and complex) were determined and compared with established biochemical changes in the concentration of nuclear estrogen receptor and RNA polymerase activity (Clark et al., 1978). Following nafoxidine there is sustained elevation of the nuclear concentration of the estrogen receptor as well as RNA polymerase I and II activities over the entire 72-hr period. From 4 to 72 hr the height of the luminal epithelial cell as well as the frequency of nuclear bodies increase at linear rates. Through steady expansion of the cytoplasmic membrane system (RER) and Golgi) the relatively undifferentiated epithelial cells of the control uterus are converted progressively into ones equipped for protein secretion. At 72 hr the effects of an estradiol implant resemble closely those observed after a single injection of nafoxidine; these include sustained nuclear receptor occupancy, elevated RNA polymerase activity, epithelial hypertrophy, and high frequency of nuclear bodies. However, after a single injection of estradiol, the luminal epithelial cells become slightly but significantly taller than the control cells and remain close to this size from 24 to 72 hr.; the frequency of nuclear bodies decreases linearly from 4 to 72 hr to fall below the control level. In addition, limited cytoplasmic autolysis is evident from 24 to 72 hr. A single injection of estradiol results in short-term nuclear receptor occupancy and elevated RNA polymerase activities which return to control levels by 24 hr. This collective evidence offers further support to the hypothesis that the duration of nuclear occupancy by the estrogen receptor is reflected in the size of the nuclear body populations in these epithelial target cells. Also during hyperestrogenization, epithelial hypertrophy is accompanied by steady formation of nuclear bodies.
We have observed three effects of deletion mutations on polyadenylation of late SV40 mRNAs. The first class of mutants lack segments (-3 to -14 bp) between the 5-AAUAAA-3' and normal poly(A) site. These mutants produce mRNas polyadenylated at new sites, downstream from the wild-type site. The poly(A) site is moved farther downstream as the deletions become larger; as a result, polyadenylation always occurs within an 11-19 nucleotide range from the AAUAAA sequence. The second class of mutants lack segments (-12 to -30 bp) between the AAUAAA sequence and the coding region of the mRNA. The poly(A) site for only one of these mutants was studied (dl1457, -12 bp). In this case, the spatial relationship between AAUAAA and poly(A) site is altered. dl1457 produces a class of mRNAs polyadenylated at the first Ca following the AAUAAA sequence, as well as other mRNAs polyadenylated farther downstream. Finally, a 16 bp deletion that includes the AAUAAA sequence prevents poly(A) addition.
(1) Systemic capsaicin treatment of neonatal and adult rats is known to affect unmyelinated afferents. However, the systemic route of administration presents several disadvantages and in order to overcome these a method was explored where a single nerve in adult rats was locally treated. (2) Sciatic nerves were exposed and a 10 mm length was soaked for 15 min in 1.5% capsaicin in vehicle or in the vehicle alone (10% Tween 80, 10% ethyl alcohol in saline). (3) Both the capsaicin solution and the vehicle caused acute block of the C compound action potential while in contact with the nerve. Removal of the solutions, however, resulted in substantial recovery of C fibre conduction. The A fibre volley was totally unaffected. (4) 13-21 days after treatment, the size of the myelinated and unmyelinated volleys evoked by maximal stimulation of the capsaicin treated nerve were unchanged but there was a 20% decrease of conduction velocity in the C fibres. (5) The ability of the maximal C volley from the treated nerve to excite cells in the spinal cord was substantially decreased (by 50%) 13-21 days after local capsaicin.
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1. Changes in the threshold for antidromic activation of C-fibre afferent terminals in the lumbar spinal cord of the decerebrate-spinalized rat have been examined. 2. The antidromic compound action potential elicited by stimulation in the dorsal horn was recorded in a sectioned dorsal root. 3. The antidromic C wave had conduction velocities and strength-duration properties similar to that described for other unmyelinated fibres. 4. The optimal position of the stimulating electrode within the spinal cord for eliciting the antidromic C wave was found to correlate with the site of entry and termination of C-afferent fibres. 5. Local stimulation within the dorsal grey of the spinal cord was shown to produce prolonged increased excitability of the C-afferent terminals in that segment. This effect was restricted to the terminals and could not be demonstrated in the stem axons of the C fibres. 6. Cutaneous afferent conditioning volleys from the sural nerve produced marked increases in the excitability of the C-afferent terminals. This effect was present at A-fibre strength sural stimulation, with no significant alteration when C-fibre strength stimulation was used. The alteration in the threshold for antidromic stimulation produced by the sural conditioning stimuli only occurred at the C-afferent terminals and not at their axons. 7. The results are discussed in terms of presynaptic inhibition of C-fibre input at a segmental level.
A survey of mammographic techniques and dosimetry in 61 NHS centres in Britain has been completed. Physical parameters measured at each centre included tube output, half-value thickness, peak kilovoltage, surface dose and percentage depth dose. Ionisation and thermoluminescence dosimetry were employed and image quality was assessed subjectively using a test phantom. Absorbed doses are given at the plane surface of an average-sized, 5 cm thick homogenous breast composed of 50% fat and 50% water. The doses fall naturally into the four combinations of molybdenum (Mo) and tungsten (W) targets and film (F) and xerox (X) receptors. The Mo/X group produced the best images of the phantom but also the highest mean dose of 3.26 cGy (rad) for a cranio-caudad (c-c) view and its use does not seem justified for asymptomatic screening. The Mo/Lo-Dose or MIN-R film combination gave a mean dose of 0.95 cGy(rad) for a c-c view whereas the W/X group gave 0.89 cGy(rad) and superior image quality. The W/F group gave the poorest image quality and its continued use for mammography is questionable.
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Cat dorsal horn was searched for all detectable units that responded to peripheral C fibre input. Fifty-seven such units were examined in detail. They were located in two main areas. One group was in the superficial laminae 1, 2, and possibly dorsal 3 (n = 29), and the other group was much deeper in laminae 5 and 6 (n = 24). Only four units were situated in the region of lamina 4. Differences were found in the responses to C fibre stimulation of these two groups, both in the optimum stimulus and in the timing of responses to repeated stimulation. Superficial units often did not respond to C fibre stimulation unless a train of two or more stimuli (10 ms apart) were applied, but when responses did occur they were usually very even and regular, with precise onset latencies on repeated stimulation. Deep units tended to need only one peripheral C fibre stimulus for excitation, but the responses were irregular with latencies fluctuating with each stimulus. Some superficial and deep units showed a steady increase in latency of the late C response on repeated stimulation. Increases of up to 80 ms after 30 s of stimulation at 1 Hz were observed. The results are discussed in terms of the neuronal connections in the dorsal horn.
1. ACTH administration (20 microgram day-1 kg-1) to sheep produces hypertension associated with a raised cardiac output and hypokalaemia. 2. The aim of the present experiments was to detail the haemodynamic changes associated with restoration of the extracellular potassium concentration in sheep with ACTH-induced hypertension. 3. After 7 days of ACTH treatment potassium chloride (10 mmol/h) was infused for 3 days to restore plasma [K+] to the pre-ACTH value. 4. ACTH reduced plasma [K+] from 4.4 +/- 0.1 to 3.2 +/- 0.2 mmol/l but 3 days of potassium chloride infusion returned plasma [K+] to 4.3 +/- 0.2 mmol/l. 5. ACTH increased mean arterial pressure from 67 +/- 2 to 88 +/- 1 mmHg in the first 7 days and it remained elevated during potassium chloride infusion (91 +/- 5 mmHg on day 10). 6. Cardiac output rose with 7 days ACTH treatment from 4.9 +/- 0.2 to 6.0 +/- 0.6 l/min but fell progressively with potassium chloride infusion to 4.9 +/- 0.3 l/min on day 10. 7. These studies suggest that potassium status or extracellular [K+] may play a role in determining the haemodynamic profile associated with steroid-induced hypertension.
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