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Biomedical subjects

C J Robinson

Publications and source records attributed to C J Robinson.

At least 91 records · Page 5Linked to original sources

Peripheral neural mechanisms of cutaneous hyperalgesia following mild injury by heat.

Pain thresholds in humans were determined for heat stimulations of the skin before and after a mild injury induced by a single conditioning stimulus (CS) of 50 degrees C and 100 sec duration. The same stimuli were delivered to the receptive fields of C fiber and A fiber mechanoheat-sensitive nociceptors (CMH and AMH nociceptors, respectively) and of low threshold warm and cold receptors in the anesthetized monkey and to the receptive fields of CMH nociceptors recorded percutaneously from the peroneal nerve of awake humans. Pain thresholds in normal skin were matched only by the response thresholds of CMH and not AMH nociceptors. Immediately following heat injury, some pain thresholds and CMH response thresholds were elevated, but by 5 to 10 min after the CS, pain and CMH thresholds were lowered to 2 to 6 degrees C below normal (hyperalgesia and nociceptor sensitization). No other type of cutaneous receptor studied exhibited changes in threshold similar to those observed for pain and for CMH nociceptors. The magnitude of hyperalgesia in humans and the magnitude of sensitization of CMH nociceptors in monkeys following heat injury were greater for hairy than for glabrous skin. The time course of the development of hyperalgesia was not altered by ischemia or conduction block in A fibers. The results support the conclusion that altered activity in CMH nociceptors is a major peripheral determinant of cutaneous hyperalgesia following a mild heat injury to the skin.

Afferent Pathways↗

Somatotopographic organization in the second somatosensory area of M. fascicularis.

The second somatosensory area (SII) of awake, untrained cynomolgus monkeys was surveyed with recordings from nearly 1,000 single neurons. A detailed somatotopographic organization could be demonstrated in SII because the majority of these neurons had contralateral, moderate to well-defined receptive fields of < 10 cm2, and because neighboring neurons possessed receptive fields that were only slightly displaced from one another. Different body regions were represented in successive anterior to posterior strips that were oriented across the parietal operculum with an anterolateral to posteromedial slant. Neurons with trigeminal receptive fields were found in the anterior portion of SII; these neurons were the only ones in SII with predominantly bilateral receptive fields (r.f.'s.). Neurons with digit or hand r.f'.s form the largest component of the map, and were located posterior to those with face r.f.s. Most of these neurons had only contralateral activation. The hand and digit region was followed in turn by the arm, the upper and lower trunk, and the hindlimb regions. Although the overall SII orientation was along an anterior-posterior gradient, recordings at individual coronal planes often demonstrated isolated sequences of receptive fields that exhibited a medial-lateral progression. The principle example of this latter gradient was seen in the forelimb region where digits one through five were represented in an overlapping sequence across the parietal operculum. Except for portions of the digit representation, neighboring sequences of neurons in SII do not form a precise topologic map of the body that is comparable to the somatotopic maps observed in areas 3b and 1. The present findings contrast with previous physiological studies of SII in the primate. These discrepancies are discussed in relation to methodological differences and in terms of distinctions used to define the boundaries of SII.

Animals↗

Organization of somatosensory receptive fields in cortical areas 7b, retroinsula, postauditory and granular insula of M. fascicularis.

The boundaries of the second somatic sensory cortex (SII) in primates are difficult to define physiologically because cutaneous stimulation activates several regions around SII that do not receive projections from the ventroposterior nucleus of the thalamus. These cortical regions, which include portions of area 7b, the retroinsular (Ri) and postauditory fields (PA), and the granular insula (Ig) are largely buried within the lateral sulcus and most lie posterior to the caudal end of the insula. The differences in somatic activity in these various cortical fields in the unanesthetized cynomolgus monkey became apparent only after the properties of many neighboring neurons could be compared. Receptive fields for area 7b and Ig neurons were generally large (< 10 cm2), with bilateral, moderately defined boundaries; some neurons in area 7b had receptive fields with labile borders as a function of wakefulness. In contrast, receptive fields for Ri neurons were generally (< 10 cm2 and contralateral, with stable, well-defined boundaries. Taken as an ensemble, the neurons in areas neighboring SII exhibited a very crude topography; but at the level of an individual neuron and its neighbor, there was never a pattern of gradual transition in peripheral receptive field locations between one unit and the next, like that seen in SII. In area 7b, this crude map was organized mediolaterally across the inferior parietal lobule and into the upper bank of the lateral sulcus, with the head represented medially and the lower trunk and hindlimb laterally. In Ri-PA, an anteroposterior organization was noted along the fundus of the lateral sulcus with the head represented anterior to the lower trunk and hindlimb. No organization was apparent in Ig. Additional sensitivity to visual stimuli was noted in the more medial aspects of area 7b that were located on the exposed inferior parietal lobule. Sensitivity to auditory stimuli was principally found in PA and occasionally in Ri. The results, especially from area 7b, are discussed with respect to previous notions about the organization of SII.

Afferent Pathways↗

Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory, and granular insular cortical areas of M. fascicularis.

Somatic response properties were determined for over 1,300 neurons isolated within and near the lateral sulci of unanesthetized and unparalyzed cynomolgus monkeys. Somatic stimuli unequivocally activated the majority of units studied in SII (93%) and in cortical fields surrounding SII: area 7b (65%), the retroinsular field (74%), and the granular insula (76%). No activation other than somatic was seen for SII neurons, and noxious somatic stimulation was rarely required. The SII units almost always responded in a rapidly adapting manner to hair or skin stimulation, but not both; however, the submodality distribution seen in SII varied as a function of peripheral receptor locations. Two small zones within SII contained neurons that responded only if the animal actively interacted with the stimulus. In contrast, one-half of the sample of neurons from area 7b unequivocally responded only to somatic stimulation. Although many neurons in the lateral parts of area 7b were vigorously activated by innocuous tactile stimulation, others demonstrated little association with an identifiable somatic submodality, had sluggish responses, required complex, noxious, visual or other non-somatic stimuli for activation, and had labile response properties and receptive fields. Indeed, the responses of some area 7b neurons suggested a possible relationship with the animal's attention towards or anticipation of a noxious or a novel somatic stimulus. Neurons within the retroinsular cortex (Ri), which receives projections from the posterior nucleus (PO), primarily responded to light tactile stimulation of rapidly adapting skin receptors; less than 3% responded to moderate or high threshold mechanical stimulation. The sensitivity to tactile stimulation in Ri closely resembled the responses of SII neurons. Neurons in the granular insula (Ig) often responded to gentle hair deflection within receptive fields covering large areas of the body. Ig and area 7b were the principle loci within the lateral sulcus that contained neurons responding to noxious stimulation. Owing to the great similarity in the somatic response properties within these areas in the awake and unparalyzed animal, the designation of cortical areas could only be made after correlating the recording sites with connectional and cytoarchitectonic analyses in the same animal. Consequently, previous physiological studies may have attributed to SII some of the response characteristics of neurons in neighboring areas.

Animals↗

Purification of carboxypeptidase B from human pancreas.

Carboxypeptidase B of the human pancreas was purified by chromatography on DEAE-cellulose and CM-cellulose columns. Two forms of the enzyme, named carboxypeptidase B1 and B2, were separated. They have similar mol.wts. (34250 +/- 590) as established by polyacrylamide-gel disc electrophoresis and by gel filtration. Carboxypeptidase B2 migrates further towards the anode in disc electrophoresis. When the amino acid content of the enzymes was analysed, carboxypeptidase B2 had four more glycine and three more aspartic acid residues than had form B1. The amino acid sequence of the human carboxypeptidase B1 differs from that of the bovine enzyme only in two places in the N-terminal 20-amino-acid sequence. The N-terminal amino acid in carboxypeptidase B1 and B2 is alanine. The peptide 'map' of the tryptic digest of carboxypeptidase B1 contained more peptides than did that of form B2. The Km, the Vmax. and the pH optimum of the cleavage of the peptide substrate hippurylarginine and the ester substrate hippurylargininic acid were similar for both enzymes. CoCl2 accelerated the peptidase activity, and cadmium acetate enhanced the esterase activity, of human carboxypeptidases B1 and B2. Urea and sodium dodecyl sulphate inhibited the enzymes.

Amino Acid Sequence↗

Prostaglandin A2 at low rates of infusion restores the antidiuretic effect of vasopressin in lithium-treated rats.

To test the effect of prostaglandin A2 (PGA2) on renal function, infusions of PGA2 (0-7 ng/kg/min), arginine-vasopressin (AVP) (1-25 ng/kg/min) and PGA2 plus AVP were administered to male rats made resistant to the antidiuretic effect of AVP by pre-treatment with lithium. In non-lithium-treated control rats, AVP had its expected antidiuretic action but in lithium-treated rats neither urinary volume nor osmolarity was changed. Prostaglandin A2 alone had no effect on urine output in lithium-treated rats; AVP plus PGA2 infused together evoked a near normal antidiuretic response. This antidiuretic action of PGA2 contrasts with the diuretic action reported by others. However, our infusion rates were 300-4000 times lower than those of other workers and it is suggested that PGs may have opposite actions on the kidney depending on their concentration. The effect of indomethacin (a blocker of prostaglandin synthesis) on urine flow was tested in five groups of rats on different régimes of liquid intake. Urine flow was reduced in the three groups with the highest urine volumes before treatment, and increased in the two groups with the lowest urinary volumes, again indicating that PGs may have both diuretic and antidiuretic actions.

Animals↗