Search PubMed⌕ Search

Biomedical subjects

W R Ferrell

Publications and source records attributed to W R Ferrell.

At least 19 recordsLinked to original sources
PubMed1992

Differences in the axon composition of nerves supplying the rat knee joint following intra-articular injection of capsaicin.

This study was used to examine the ultrastructure of articular nerves supplying the medial aspect of the rat knee joint following injection of capsaicin into the synovial cavity. One week after the intra-articular injection of 0.2 ml of 1% capsaicin solution there was significant reduction in the number of unmyelinated fibres. Two weeks post-injection this appeared to recover and by 4 weeks post-injection no further changes were observed. Myelinated fibres were unaffected by capsaicin injection. This procedure provides an effective means of producing short-term degeneration of unmyelinated fibres innervating the knee joint.

Animals↗
PubMed1992

Acute inflammation enhances substance P-induced plasma protein extravasation in the rat knee joint.

Acute inflammation of the rat knee joint was induced by intra-articular injection of 2% carrageenan. Intra-articular perfusion of the inflamed joint with substance P (SP) exacerbated the inflammatory condition as assessed by the degree of plasma protein extravasation into the synovial cavity. Protein extravasation induced by SP was enhanced and more persistent in the inflamed rat knee compared to normal animals. The time course of the response in the inflamed rat knee was related to SP concentration whilst the persistency of the response was positively correlated with the initial level of joint inflammation.

Animals↗
PubMed1992

Age-dependent changes in position sense in human proximal interphalangeal joints.

Using a position matching paradigm, the ability of subjects to detect displacements at the proximal interphalangeal joint of the index finger was tested. These displacements were imposed at an angular velocity of 2 degrees per minute which is below the threshold for movement detection. An older group of subjects whose mean age (+/- s.e.m.) was 56.6 +/- 3.2 years showed significantly poorer performance in detecting the position of the index finger than a group of younger subjects (23.7 +/- 0.5 years). Analysis of the correlation between age and magnitude of matching error gave a positive correlation coefficient of 0.466 which was statistically significant. However, there was no systematic bias in judgements of finger position by the older group. These results indicate that the sense of position of the fingers decrements with age.

Adult↗
PubMed1992

Contribution of joint and muscle afferents to position sense at the human proximal interphalangeal joint.

Experiments were carried out to examine the perceived position of the human index finger about the proximal interphalangeal joint. In protocol I, the finger was moved from an intermediate position at velocities ranging from 200 deg/min to 2 deg/min, then held still at one of three positions. The subject's task was visually to align a finger silhouette that was coaxial with the joint to the kinaesthetically perceived position of the unseen finger. Judgements of position were found to be quite accurate, and unaffected by previous velocity. Protocol II showed that although the direction of joint displacements of 0.01 and 0.1 deg could not be detected at any velocity, 1 deg could be detected at 200 deg/min and 10 deg at 20 and 2 deg/min. In protocol III the finger was moved at 2 deg/min and maintained at either 105 or 175 deg. It was found that the position of the unanaesthetized finger was quite accurately known, but with digital nerve block, subjects clearly perceived the finger to be at the mid-position (approximately 130-150 deg). This suggests that the absence of joint and cutaneous afference is interpreted by the CNS as indicating mid-position. The slight bias of the sensed position towards the objective position shown by the results also indicates that muscle afferents can provide a crude signal related to joint position. This finding was further supported by the observation that splinting the distal interphalangeal joint into flexion resulted in flexion bias in the perceived angle of the proximal interphalangeal joint. Anaesthesia of the middle finger, thumb and distal portion of the index finger (leaving proximal joint unaffected), had little effect on position matching performance, suggesting that the large error in position sense during anaesthesia of the whole finger is due to loss of afference specifically related to the proximal interphalangeal joint, and not due to loss of non-specific facilitatory influences from cutaneous and joint afferents. The results argue for an important proprioceptive role for joint afferents at finger joints.

Adult↗
PubMed1992

Position sense at the proximal interphalangeal joint is distorted in patients with rheumatoid arthritis of finger joints.

The results of this investigation demonstrate, using a position matching paradigm, that the ability of subjects to detect changes in the position of the proximal interphalangeal joint is impaired in patients with rheumatoid arthritis affecting this joint. In this group there is a systematic flexion bias in position judgements compared to an age- and sex-matched control group. This bias becomes progressively more pronounced at more extended positions. These results suggest that chronic inflammatory joint disease significantly alters proprioceptive sensations at finger joints and this may be due to the loss or distortion of afferent feedback from mechanoreceptors innervating the affected joint.

Adult↗
PubMed1992

Changes in synovial PO2 and blood flow in the rabbit knee joint due to stimulation of the posterior articular nerve.

1. Experiments were performed to measure the partial pressure of oxygen in the synovial fluid (Ps,O2) of the normal rabbit knee joint and assess the extent to which this varied with changes in knee joint blood flow. 2. With the hypodermic needle oxygen electrode sited just within the synovial cavity, Ps,O2 values ranged from 25 to 72 mmHg with a mean of 48.2 +/- 3.1 (S.E.M.; n = 18). 3. Ps,O2 was found to decrease with increasing depth of penetration of the oxygen electrode. Lowest values were observed close to the articular cartilage. 4. Electrical stimulation of the posterior articular nerve (PAN) of the knee resulted in vasoconstriction of knee joint blood vessels which was accompanied by a decrease in Ps,O2. The frequency-response and voltage-response profiles to electrical stimulation of PAN, although differing in magnitude, showed a high degree of correlation between blood flow and Ps,O2. 5. As judged by the conduction velocity, the vasoconstrictor response to nerve stimulation was mediated by unmyelinated nerve fibres, presumed to be sympathetic postganglionic fibres. 6. In view of the low Ps,O2 values occurring deep within the joint, avascular structures such as cartilage could be subject to injury if sustained reduction in synovial blood flow occurred. This could be a contributory factor in the pathogenesis of degenerative and inflammatory joint diseases.

Animals↗
PubMed1992

Acute joint inflammation alters the adrenoceptor profile of synovial blood vessels in the knee joints of rabbits.

Experiments were carried out to examine the effect of acute inflammation, induced by intra-articular injection of 2% carrageenan, on the response of articular blood vessels in the knee joints of rabbits to adrenoceptor agonists. The responses to noradrenaline, phenylephrine, clonidine, UK-14304, and isoprenaline were examined 24 hours after carrageenan injection and compared with those of normal animals. Antagonists specific for alpha 1 and alpha 2 were used to identify the adrenoceptors through which the responses were mediated and to examine if carrageenan treatment altered the adrenoceptor profile of these blood vessels. The evidence suggests that in the carrageenan treated animals there is a reduction in the alpha 1 response with an associated increase in the alpha 2 response. A decrease in the number or affinity of alpha 1 adrenoceptors is indicated by the shift to the right of the noradrenaline and phenylephrine dose/response curves, whereas an increase in alpha 2 affinity or number is suggested by the associated leftward shift in the alpha 2 adrenoceptor agonist curves. This change in receptor profile appears to arise as a direct result of carrageenan induced joint inflammation.

Acute Disease↗
PubMed1991

Time course of substance P-induced protein extravasation in the rat knee joint measured by micro-turbidimetry.

Intra-articular perfusion of the rat knee joint with substance P (SP) resulted in protein extravasation into the synovial cavity. This response was tested over a range of SP concentrations from 100 pM to 100 microM. The response was dose dependent from 10 nM to 10 microM, with each dose producing a steady rise of the protein content in the fluid aspirated from the synovial cavity for 12-16 min and then fell sharply again over an equivalent period despite continuing perfusion with SP. Concentrations below 10 nM gave rise to very brief increases in protein extravasation whose magnitude differed little over the range of 100 pM to 10 nM but differed significantly from control (saline) perfusion.

Animals↗
PubMed1991

Specific neurokinin receptors mediate plasma extravasation in the rat knee joint.

1 Plasma extravasation in the rat knee joint was induced by intra-articular injection of neurokinins and specific neurokinin receptor agonists. 2 Pronounced plasma extravasation was produced by substance P (SP, 4-185 microM) and to a lesser extent by neurokinin-B (NKB, 83-413 microM), whereas neurokinin-A (NKA, 88-440 microM) and calcitonin gene-related peptide (CGRP, 26-130 microM) had no significant effect. 3 The specific neurokinin1 receptor agonist [Sar9, Met(O2)11]-substance P (NK1 agonist) in doses of 0.4-70 microM appeared to be more potent than SP in eliciting plasma extravasation. The neurokinin2 receptor agonist [Nle10]-neurokinin A4-10 (NK2 agonist) was not effective at 70 microM but produced a small and significant effect at 330 microM, whereas the neurokinin3 receptor agonist [MePhe7]-neurokinin B (NK3 agonist) was without effect at 40 microM or 400 microM. 4 Injections of SP or NKA into the synovial cavity of the rat knee were equally effective in producing marked plasma extravasation in remote sites such as the forelimb and hindlimb paws. 5 Co-administration experiments showed that the effects of SP were synergistic with NKA or the NK1 receptor agonist, but not with CGRP or the NK2 receptor agonist. 6 The rank order of potency was NK1 agonist greater than or equal to SP greater than NKB greater than NK2 agonist suggesting that NK1 receptors mediate plasma extravasation in the rat knee joint.

Animals↗
PubMed1991

Neurogenic component of different models of acute inflammation in the rat knee joint.

This study was performed to investigate whether different models of acute joint inflammation showed a neurogenic component and to establish whether this is mediated through sensory afferent or sympathetic efferent nerve fibres. Intra-articular injection of 2% carrageenan, 20 micrograms substance P, 1% formalin, and 2% urate all produced an inflammatory response. Prior surgical denervation of the joint significantly inhibited this response in the carrageenan and formalin models, but not the others. Pretreatment of the joint with 1% capsaicin (about one week previously) significantly reduced the inflammatory response in all models except formalin. In animals pretreated long term with reserpine (to deplete sympathetic nerve endings of their neurotransmitters) significant reductions occurred in the inflammatory responses to substance P and urate. Intraarticular injection of compound 48/80 produced a marked inflammatory response, which was only significantly reduced by capsaicin pretreatment. These results suggest that both the formalin and carrageenan models of inflammation depend to some extent on the integrity of the sensory innervation of the joint, and thus have a neurogenically mediated component to the inflammatory process they generate. In these models there seems to be little contribution from sympathetic efferent fibres. Each model of inflammation showed a different pattern of response to the pretreatments, suggesting that the mediators of the inflammatory process may differ in each case.

Animals↗
PubMed1990

Mediators of substance P-induced inflammation in the rat knee joint.

Substance P (SP) injected into the synovial cavity of the rat knee resulted in an inflammatory response as measured by plasma protein extravasation into the joint capsule. This response was dose dependent over the range of approximately 4 microM to approximately 200 microM. Part of this inflammatory response was mediated via mast cells as pre-treatment of the animals with a mast cell degranulator (compound 48/80) resulted in a 66% reduction of the response. A direct effect of SP on the vascular receptors may also contribute to the inflammatory response as pre-treatment with the substance P antagonist (SPA) D-Pro4 D-Trp7,9,10 SP4-11 also reduces the inflammatory response. Intra-articular injections of the H1 blocker diphenhydramine or the H2 blocker cimetidine significantly blocked the SP-induced inflammatory response. The 5-hydroxytryptamine (5-HT) antagonist methysergide proved to be even more potent in blocking the SP-induced inflammatory response. No synergistic inhibition was observed with combinations of the different antagonists. Intra-articular injections of 5-HT elicited a much more pronounced inflammatory response than that produced by a 10-fold higher concentration of histamine. The results suggest that SP produces increased vascular permeability partly via direct actions on the blood vessels and partly via mast cells. The inflammatory response occurring via mast cells appears to be mediated by histamine and to a greater extent by 5-HT.

Animals↗
PubMed1990

The role of the endothelium in mediating the actions of ATP, adenosine and acetylcholine on flow through blood vessels in the rabbit knee joint.

1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke solution, was used to investigate the presence of purinoceptors and the role of endothelium within articular blood vessels. 2. The basal tone of the blood vessels was not affected by adenosine or acetylcholine. Adenosine 5'-triphosphate (ATP) injection produced vasoconstriction which was unaffected by removal of the endothelial layer, but diminished by alpha, beta methylene ATP, a compound which desensitizes P2-purinoceptors. 3. When knee joint blood vessel tone was raised by perfusion with vasopressin (10(-8) M) or 5-hydroxytryptamine (10(-5) M), acetylcholine, ATP and adenosine were all found to induce concentration-dependent relaxation of these vessels. ATP was found to have a dual effect of transient constriction followed by longer-lasting dilatation. 4. 3-Methylxanthine, a P1-purinoceptor antagonist significantly reduced the relaxation response to adenosine but had no effect on the vasodilator effect of ATP. 5. Removal of the endothelial layer virtually abolished the vasodilator effects of acetylcholine and ATP but not adenosine. 6. These results demonstrate that articular blood vessels supplying the rabbit knee contain P1-purinoceptors located on the vascular smooth muscle which mediate vasodilatation. P2-purinoceptors mediating a constrictor effect are also present on this smooth muscle. It is likely that the vasodilator effect of ATP is mediated via P2-purinoceptors located on the endothelial layer.

Acetylcholine↗
PubMed1990

Fourier analysis of the relation between the discharge of quadriceps motor units and periodic mechanical stimulation of cat knee joint receptors.

It has been widely assumed that joint receptors contribute to the reflex regulation of movement and posture, although there have been few clear demonstrations of joint-mediated reflex actions on alpha-motoneurones other than those attributable to flexor reflex afferents. The present study extends our recent work on joint-mediated reflexes by using Fourier analysis of spike train interactions to demonstrate that restricted mechanical activation of a small number (one to five) of knee joint receptors by localized indentation of the joint capsule can modify the firing pattern of quadriceps motoneurones in decerebrated cats. The modulation of this discharge pattern can be reversibly abolished by application of droplets of lignocaine directly to the joint nerve and consequently can be attributed unambiguously to articular afferents. Activation of single joint afferents could on occasion produce changes in motor unit firing patterns, but usually activation of two or more was required before secure effects were observed. Increasing the intensity of indentation (resulting in activation of greater numbers of joint receptors) increases the strength of coupling between joint afferent input and motor unit responses, although the relationship is not linear. The relation between the discharge patterns of pairs of motor units was also examined, and it was found that significant coupling occurred at the stimulus frequency, superimposed on a 'background' coupling from unidentified sources. The phase relationship between pairs of motor units was not affected by the periodic stimulus. However, it was observed that if two motor units were firing independently of one another in the absence of capsule probing, maintained capsular indentation produced a striking synchronization between the discharges of the two motor units. These experiments show strong joint-mediated reflex effects on motor unit firing indicating that joint receptors may have an important role to play in motor control.

Action Potentials↗
PubMed1990

Responses of blood vessels in the rabbit knee to electrical stimulation of the joint capsule.

1. An in vitro preparation of the rabbit knee joint, perfused with oxygenated Locke's solution, was used to study the response of articular blood vessels to electrical stimulation of the joint capsule. 2. Using trains of stimulus pulses of different durations, frequency-response curves were obtained. Electrical stimulation always produced vasoconstriction of joint blood vessels, which increased as a function of both frequency and pulse width. 3. This vasoconstrictor response was neurally mediated as it was markedly inhibited after addition to both bath and perfusate of tetrodotoxin. In addition, the response to field stimulation of the capsule was virtually abolished in animals pretreated with reserpine which depletes sympathetic nerve endings of noradrenaline. 4. The response to electrical stimulation was substantially reduced by the alpha-adrenergic antagonist phenoxybenzamine (10(-5) M), the alpha 1-blocker prazosin (10(-6) M), and by guanethidine (10(-5) M) which inhibits the release of noradrenaline, ATP and neuropeptide Y from sympathetic nerve endings. 5. The attenuation of the vasoconstrictor response to field stimulation by prazosin (10(-6) M) was little altered by addition of the alpha 2-adrenoceptor blocker rauwolscine (10(-6) M) to the perfusate. 6. alpha, beta-Methylene ATP (10(-6) M), a P2-purinoceptor desensitizer, had no effect on the vasoconstrictor response to electrical stimulation. 7. These results indicate that the vasoconstrictor response to electrical stimulation of the rabbit knee joint capsule is mediated via noradrenaline acting upon alpha 1-adrenoceptors.

Adenosine Triphosphate↗
PubMed1990

Alterations in cat knee joint blood flow induced by electrical stimulation of articular afferents and efferents.

1. Experiments were performed in cats anaesthetized with pentobarbitone. Laser Doppler flowmetry was used to assess the responses of knee joint blood vessels to nerve stimulation under control conditions and in the presence of different adrenoceptor antagonists in order to establish the nature of neurotransmitters released from articular nerve fibres. 2. The posterior articular nerve (PAN) supplying the knee was stimulated at different intensities, and frequency-response curves were obtained. In fourteen animals electrical stimulation of PAN produced an initial vasoconstriction during stimulation which in eight of these was followed by a prolonged dilatation on cessation of stimulation. The constrictor response was increased as a function of frequency but was little altered with increasing intensity beyond a threshold level. 3. The constrictor response to electrical stimulation of PAN was markedly reduced by the alpha-adrenergic antagonist phentolamine (10(-5) M, the alpha 1-blocker prazosin (10(-5) M), and guanethidine (10(-5) M) which inhibits the release of noradrenaline, ATP, and neuropeptide Y from sympathetic nerve endings. 4. The constrictor response to PAN stimulation was unaffected by the alpha 2-blocker rauwolscine and the P2-purinoceptor desensitizer alpha,beta-methylene ATP. 5. The dilator response was due to activation of afferent fibres as it could also be produced by direct electrical stimulation of the L7 dorsal roots. 6. The dilator response to stimulation of PAN or the L7 dorsal root was reduced by prior intra-articular injection of 100 micrograms of the substance P antagonist D-Pro4-D-Trp7,9,10-SP4-11. 7. These results suggest that the vasoconstrictor response to electrical stimulation of PAN is most likely to be mediated via noradrenaline acting mainly upon alpha 1-adrenoceptors. As the dilator response to articular nerve stimulation is reduced by a substance P antagonist, the mediator inducing this response may be substance P or a related neurokinin.

Adenosine Triphosphate↗
PubMed1990

Responses of bone and joint blood vessels in cats and rabbits to electrical stimulation of nerves supplying the knee.

1. Experiments were performed to assess the extent to which knee joint blood flow in cats and rabbits is affected by electrical stimulation of the nerve supply to the knee. 2. Absolute changes in blood flow were measured using the radiolabelled microsphere (approximately 15 microns) technique whilst relative changes in blood flow were assessed using laser Doppler flowmetry. 3. Despite deep general anaesthesia, sympathetic nerve fibres innervating cat knee joint blood vessels showed marked 'tone'. 4. Blood flow to the joint capsule (synovium and overlying fibrous and areolar tissues) was substantially reduced (by approximately 90% in the cat and approximately 45% in the rabbit) during electrical stimulation of the articular nerve supply. 5. The percentage change in the laser Doppler flowmeter signal did not differ significantly from the percentage change in blood flow measured by microsphere technique. 6. Blood vessels in the cancellous bone of the distal femur (condyles) and proximal tibia (plateau) appear to be innervated by vasoconstrictor fibres which reach their effectors via the articular nerves. However, the cortical bone and red marrow of the diaphysis of the femur do not receive such innervation. 7. The potency of the vasoconstrictor influences acting on joint blood vessels could be of relevance in the pathogenesis of inflammatory joint diseases.

Anesthesia, General↗
PubMed1990

Responses of blood vessels in the rabbit knee to acute joint inflammation.

These experiments examined the responses of articular blood vessels in the rabbit knee to induction of acute joint inflammation by intraarticular injection of 4% kaolin suspension. This produced an inflammatory response, which became evident about four hours after injection. Electrical stimulation of the nerve supply to the knee joint before induction of inflammation produced a biphasic response--an initial vasoconstriction during the stimulation phase followed by dilatation after stimulation stopped. These responses were followed up for eight hours and it was noted that the constrictor response became progressively greater, producing a further 19% decrease in blood flow during nerve stimulation about three hours after the injection of kaolin. The sensitivity of postjunctional alpha adrenoceptors, however, showed still greater increase in the inflamed joint as close intraarterial injection of 10(-6) M adrenaline produced an additional 30% reduction in blood flow four hours after kaolin injection compared with the control response. Possibly, the smaller enhancement of the constrictor response to nerve stimulation in the inflamed joint may reflect sensitisation of prejunctional alpha adrenoceptors in addition to the effects exerted on postjunctional alpha adrenoceptors by the inflammatory process. The dilator response also increased over eight hours, though this rise was less marked. These findings indicate that even over the limited time span of the experiments, significant alterations occurred in factors which influence the calibre of articular blood vessels.

Acute Disease↗