PubMed Health⌕ Search

Biomedical subjects

S N Raja

Publications and source records attributed to S N Raja.

At least 19 recordsLinked to original sources
PubMed1999

Sympathectomy decreases formalin-induced nociceptive responses independent of changes in peripheral blood flow.

The present experiments studied the effect of surgical sympathectomy on mechanical paw withdrawal thresholds and formalin-induced pain behaviors (FIPB) and tested if the effect of sympathectomy on FIPB is dependent on changes in peripheral blood flow. Compared to sham-operated animals, surgical sympathectomy decreased second phase FIPB but did not affect paw withdrawal thresholds to mechanical stimuli. In sympathectomized and sham-operated animals, subcutaneous intraplantar injection of the nonadrenergic vasoconstrictor angiotensin II (20 microl, 1 mM) or the nonadrenergic vasodilator hydralazine (20 microl, 1 mM) prior to formalin injection decreased and increased peripheral blood flow, respectively. In sympathectomized animals, pretreatment with angiotensin II inhibited the increase of peripheral blood flow following formalin injection when compared to animals pretreated with saline or hydralazine. In sham-operated animals, pretreatment with hydralazine or angiotensin II did not alter vasodilation after formalin injection when compared to pretreatment with saline. Pretreatment with vasoactive drugs had no effect on the sympathectomy-induced decrease in FIPB. It is concluded that sympathectomy decreases FIPB by mechanisms that are independent of sympathectomy-induced changes in peripheral blood flow. The formalin test is an easy, reliable model that can be used to study the mechanisms by which the sympathetic nervous system modulates pain processing.

Animals↗
PubMed1998

Neuropathic pain following partial nerve injury in rats is suppressed by dietary soy.

Some humans with partial nerve injury present a syndrome of neuropathic sensory disorders which depend on the sympathetic activity (sympathetically-maintained pain, SMP). Several years ago we introduced a rat model for SMP, produced by tightly ligating 1/3-1/2 of the sciatic nerve, leading to a partial denervation of the hindpaw (Partial Sciatic Ligation, PSL model) [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 (1990) 245-250]. After working with this model for several years we encountered difficulties in replicating it although rat strain, vendor, gender, age and weight, surgical approach and sensory testing procedures were not changed. We report here that this variability can be attributed, at least in part, to the diet the animals consumed. Rats fed perioperatively with soy-containing diets expressed significantly weaker neuropathic sensory disorders compared to rats fed on soy-free diets. We conclude that diet may greatly affect experimental outcome in the PSL model.

Animals↗
PubMed1998

Pain and quality of life following radical retropubic prostatectomy.

PURPOSE: We assess pain and quality of life following radical retropubic prostatectomy and determine whether intraoperative anesthetic management has any long-term effects on outcomes. MATERIALS AND METHODS: A total of 110 patients undergoing radical retropubic prostatectomy were randomly assigned to receive epidural and/or general anesthesia. Patients responded to a questionnaire mailed 3 and 6 months following surgery that assessed prostate symptoms, pain related to surgery, quality of life and mood. RESULTS: No long-term effects of anesthesia were observed. Of the 103 respondents (94%) at 3 months 49% had some pain related to surgery. Although pain was not related to anesthesic technique, patients who had it at 3 months used significantly more pain medication on postoperative day 3. Pain at 3 months was mild, averaging 1.5 on a scale of 0 to 10, and associated with poor perceptions of overall health (p <0.02), and reduced physical (p <0.01) and social (p <0.01) functioning. Pain at 3 months was associated with higher levels of preoperative anxiety (p <0.05). At 6 months 36 of 90 patients (35%) had some pain related to surgery and the impact was similar. CONCLUSIONS: Long-term effects of intraoperative anesthesic technique were not apparent. Mild pain following radical retropubic prostatectomy was common and associated with reduced quality of life, particularly social functioning. Affective distress, particularly anxiety, before surgery and use of pain medications following surgery may be predictors of chronic pain following radical retropubic prostatectomy.

Affect↗
PubMed1996

Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue.

Peripheral nerve injury may lead to a chronic neuropathic pain state that results from an increase in excitability of central neurons. This central sensitization is mediated via an N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). As NO is suggested to play a role in nociceptive transmission following nerve injury, we examined for altered NO synthase activity at multiple levels of peripheral and spinal neural tissue in a rat model of neuropathic pain. Peripheral neuropathy was induced in rats (N = 12) by ligation of the left L5 and L6 nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical stimuli confirmed the presence of a neuropathic pain state. Samples of the lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nerves were obtained from the lesioned and contralateral sides at 2 and 4 weeks after neuropathic surgery (N = 6 per group). In the lumbar spinal cord, a bilateral decrease in nitric oxide synthase (NOS) activity was observed 2 and 4 weeks after neuropathic surgery. NOS activity was increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activity in the DRG may be an early mechanism for inducing more central changes. The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from increased NO production in the spinal dorsal root ganglia. Multiple alterations in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting from peripheral nerve injury. (Preliminary results of these studies have been presented in abstract form at the annual meetings of the Society for Neuroscience, 1994, and the American Society of Anesthesiologists, 1994).

Analysis of Variance↗
PubMed1996

alpha-Adrenoceptor mechanisms of thermoregulation during cold challenge in humans.

1. Previous studies on the thermoregulatory effects of alpha-adrenoceptor antagonists have been performed primarily in animals and the findings have been inconsistent. There is evidence for thermoregulatory impairment by alpha-adrenergic antagonists in humans not exposed to cold, but the effects of alpha-adrenergic blockade during cold challenge have not been investigated. 2. Fourteen healthy human volunteers (seven elderly, aged 55-68 years and seven young, aged 19-27 years) were studied on three separate days and received three randomly assigned treatments; (i) control (no drug), (ii) low-dose phentolamine and (iii) high-dose phentolamine. On each day cold intravenous saline (4 degrees C) was given until both vasoconstriction and shivering were triggered or a maximum fluid volume (40 ml/kg) was delivered. Core temperature, peripheral vasoconstriction and metabolic heat production were measured. 3. The alpha-adrenoceptor antagonist caused a dose-dependent inhibition of vasoconstriction in the elderly but did not impair vasoconstriction in the young subjects at the doses that were given. Shivering and metabolic heat production were unaffected by alpha-adrenergic blockade in the elderly or in the young. 4. These findings illustrate the selective inhibition of vasoconstriction (but not shivering) by alpha-adrenoceptor antagonism in elderly individuals. Compared with the young, the elderly are more sensitive to the effects of alpha-antagonists, perhaps due to downregulation of the alpha-adrenoceptor. These findings lead us to conclude that thermoregulatory vasoconstriction is alpha-adrenergically mediated, and this response is attenuated by alpha-adrenoceptor blockade in elderly humans.

Adrenergic alpha-Antagonists↗
PubMed1995

Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin.

1. Mechano- and heat-sensitive A fibre nociceptors (AMHs) and C fibre nociceptors (CMHs) in hairy skin (forty-six AMHs and twenty-one CMHs) and in glabrous skin (fifty-nine AMHs and ten CMHs) of anaesthetized monkeys were tested with a 30 s, 53 degrees C heat stimulus, delivered by a laser thermal stimulator (0.1 s rise time, 7.5 mm diameter). 2. Two types of heat response were observed in hairy skin AMHs. Type I AMHs had a peak discharge towards the end of the stimulus, response latencies to heat of up to several seconds, a median heat threshold greater than 53 degrees C, and a mean conduction velocity of 25 m s-1 (n = 33). Type II AMHs had a peak discharge within 1-3 s, a mean response latency of 120 ms, a median heat threshold of 46 degrees C, and a mean conduction velocity of 15 m s-1 (n = 13). Type I AMH fibres were sensitized to heat, whereas heat responses of type II AMHs were suppressed following the intense heat stimulus. 3. In glabrous skin, only type I AMHs were found. The absence of type II AMHs is consistent with the absence of first pain to heat in glabrous skin. 4. C fibre nociceptors in hairy skin had a peak discharge near stimulus onset, a mean response latency of 100 ms and a median heat threshold of 41 degrees C. Heat responses of CMHs in glabrous skin were not significantly different from those in hairy skin. 5. Only type II AMHs had response latencies that were short enough to explain first pain to heat. Heat thresholds of type II AMHs were significantly higher than those of CMHs. 6. These results suggest two different heat transduction mechanisms in nociceptive afferents. For one, heat energy is quickly transduced into action potentials, and the peak discharge is reached soon after stimulus onset. For the other, the transduction of heat is distinctly slower, and the peak discharge occurs near the end of the stimulus. Chemically mediated sensitization may be involved in the second transduction mechanism.

Animals↗
PubMed1995

Intraoperative blood loss during radical retropubic prostatectomy: epidural versus general anesthesia.

OBJECTIVES: There are conflicting reports on the influence of different anesthetic techniques, such as regional versus general anesthesia, on intraoperative blood loss. The purpose of this study was to elucidate the effects of anesthetic technique on intraoperative blood loss in men undergoing radical retropubic prostatectomy (RRP). METHODS: One hundred patients undergoing RRP for prostate cancer were randomly assigned to receive either epidural anesthesia (EA), combined epidural and general anesthesia (EG), or general anesthesia alone (GA). Intraoperative blood loss was calculated by using a formula that accounted for the volume and hematocrit of the fluid suctioned from the surgical field, blood absorbed on surgical pads, and the patient's hematocrit. RESULTS: Mean blood loss in the EA group (1490 +/- 90 mL; mean +/- SEM) was significantly less than mean blood loss in both the EG group (1810 +/- 100 mL) and the GA group (1940 +/- 130 mL) (P = 0.01). Blood loss was not different between the EG and the GA groups (P = 0.7). Significantly less blood was transfused during surgery in the EA group (730 +/- 50 mL) compared with the EG (960 +/- 60 mL) and GA (950 +/- 70 mL) groups (P = 0.02). CONCLUSIONS: Similar blood loss in patients receiving general anesthesia, either alone or when combined with epidural anesthesia, implies that epidural anesthesia did not reduce bleeding, but, rather, that general anesthesia increased blood loss.

Anesthesia, Epidural↗
PubMed1995

Role of alpha-adrenoceptors in the maintenance of core temperature in humans.

1. Although alpha-adrenoceptor antagonists have been shown to induce core hypothermia in animals, it is unclear whether the primary mechanism is increased heat loss or decreased heat production. Furthermore, studies have not been performed in humans to determine the role of alpha-adrenoceptors in the maintenance of core temperature. 2. alpha-Adrenoceptor blockade was achieved with three doses of phentolamine given by random assignment on three different study days in five male and five female healthy subjects. Core temperature, mean skin-surface temperature, fingertip capillary blood flow and metabolic heat production were measured. Dose-response curves were plotted for all measured variables, and males and females were compared to identify potential gender differences. 3. Core temperature decreased with all doses of phentolamine. At the completion of the phentolamine infusion, the decrease in core temperature was more significant with high-dose (0.3 +/- 0.1 degrees C, P = 0.03) and with medium-dose (0.2 +/- 0.0 degrees C, P = 0.05) phentolamine than with low-dose phentolamine (0.1 +/- 0.0 degrees C). The maximum core temperature decrease during the study was more significant with high dose (0.6 +/- 1 degrees C) than with medium (0.3 +/- 1 degrees C, P = 0.04) or low (0.3 +/- 1 degrees C, P = 0.005) doses. Mean skin-surface temperature was increased with all doses. Fingertip blood flow was increased (approximately 60% above baseline) with the medium and high doses, but was unchanged with the low dose. Total body oxygen consumption was unchanged regardless of dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1995

Arteriovenous differences in plasma concentrations of catechols in rats with neuropathic pain.

BACKGROUND: Alterations in cutaneous temperature, sweating, and cutaneous blood flow in patients with pain states, such as reflex sympathetic dystrophy and causalgia, have been interpreted as evidence for exaggerated sympathetic outflow. It was determined whether pain behavior in a rat model of sympathetically maintained pain is associated with alterations in regional sympathoneural function. METHODS: Peripheral neuropathy was induced in 29 Sprague-Dawley rats by ligation of the left L5 and L6 spinal nerves. Sixteen other rats had sham surgery (nerve exposure without ligation). Animals were tested for behavioral signs of allodynia (decreased paw withdrawal thresholds to mechanical stimuli) at 2 and 4 weeks after the surgery. Arterial and iliac venous blood samples (left, affected; right, control) were obtained at 2 weeks (NP2, n = 14) and 4 weeks (NP4, n = 15) after neuropathic or sham (n = 8 at 2 and 4 weeks) surgery. Plasma concentrations of dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, norepinephrine, and the intraneuronal norepinephrine metabolite, 3,4-dihydroxyphenylglycol, were analyzed in arterial and left and right iliac venous samples. RESULTS: A decrease in paw withdrawal threshold was observed in neuropathic (NP2 and NP4) but not sham-operated rats. Affected and control limbs did not differ in arteriovenous differences in concentrations of dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, or 3,4-dihydroxyphenylglycol. No differences were observed between sham-operated and neuropathic animals in these arteriovenous increments. In contrast, affected limbs of NP2 rats had a reduced arteriovenous increment in norepinephrine concentrations, compared to that in the control side (P < 0.05). CONCLUSIONS: No neurochemical evidence of sympathetic hyperactivity is observed in the rat model of neuropathic pain; if anything, norepinephrine release is decreased in the affected limb. Autonomic disturbances in neuropathic pain are therefore more likely the result of receptor supersensitivity than increased local sympathoneural traffic.

Animals↗
PubMed1995

Role of the sympathetic nervous system in acute pain and inflammation.

The sympathetic nervous system serves not only to regulate involuntary functions, but also appears to play an important part in modulating sensory processing. While studies in animal models of neuropathic pain and clinical observations point to a role of the sympathetic nervous system in certain chronic pain states, the function of the sympathetics in postoperative pain and inflammation is debatable. Behavioural studies in rats point to a contribution of the sympathetic postganglionic terminal in the hyperalgesia of cutaneous inflammation and the severity of arthritis. An indirect effect of noradrenaline and inflammatory mediators via the release of prostaglandins has been postulated. Neurophysiological studies of nociceptors in rats and psychophysical studies in humans have failed to provide confirmatory evidence for the role of the sympathetic efferents in inflammatory pain and hyperalgesia. The clinical significance of the potential interaction of the sympathetic nervous system and the somatic afferent system needs further investigation.

Acute Disease↗
PubMed1994

Reflex cutaneous vasoconstriction during cold pressor test is mediated through alpha-adrenoceptors.

The effects of the cold pressor test on the coronary circulation have been clearly defined but the effects on the peripheral vasculature are less well understood. To measure the peripheral vasomotor response during cold pressor test perfusion in the upper extremity contralateral to the cold immersion was assessed by laser Doppler flowmetry and skin-surface temperature gradients. To identify the mechanism of vasoconstriction, cold pressor test was performed before and after the administration of phentolamine, an alpha-adrenoceptor antagonist. Vasoconstriction during cold pressor test was demonstrated by both skin-surface temperature gradients and by laser Doppler flowmetry. This vasoconstrictor response was significantly attenuated by the administration of phentolamine. The results demonstrate that the cold pressor test induces an alpha-adrenoceptor mediated vasoconstriction in the peripheral vasculature.

Adult↗
PubMed1994

Multidimensional health locus of control beliefs and psychological health for a sample of mothers.

Five multidimensional health locus of control (MHLC) types for 772 women whose children are enrolled in a longitudinal study of their health and development were identified. The MHLC is composed of an internal and two external dimensions (chance and powerful others). The five independent MHLC clusters were: pure internal; believer in control; pure chance; yea-sayer; and nay-sayer. Women with high scores on the three dimensions of the MHLC (yea-sayer) compared with the rest of the sample were significantly more likely to be from a lower socio-economic status, score lower on a general verbal intelligence test and higher on the Neuroticism and Lie Scales of the Eysenck Personality Inventory. They rated their overall health as significantly poorer, and reported more symptoms of depression compared with the other groups. A pure internal locus of control was strongly associated with the report of good health. Women with a strong belief in internal and powerful other loci of control were significantly more likely to have received treatment for their depression compared with other groups. Help-seeking for children's problem behaviour did not vary significantly with MHLC groups. The present study replicated five out of six MHLC types identified in an earlier study, and established the external validity of the MHLC types on measures of health status. The findings support the use of MHLC types in future research on health locus of control.

Adolescent↗
PubMed1994

Postoperative morbidity is similar in patients anesthetized with epidural and general anesthesia for radical prostatectomy.

OBJECTIVES: To compare the effect of epidural and general anesthesia on the postoperative course and complication rate in patients undergoing radical prostatectomy. METHODS: Ninety-eight men scheduled for radical retropubic prostatectomy (RRP) were randomly assigned to receive epidural anesthesia only (EA, n = 34), combined epidural and general anesthesia (EG, n = 33) or general anesthesia only (GA, n = 31). In the EA group, epidural anesthesia was induced and maintained with bupivacaine. In the EG group, patients received epidural bupivacaine after the induction of general anesthesia. In the GA group, anesthesia was induced with morphine and maintained with isoflurane. In the postoperative period, epidural patient-controlled analgesia (PCA) was maintained in all patients for 3 to 5 days. Patients were evaluated throughout the hospitalization period and at 3, 6, and 12 weeks following surgery. RESULTS: The three groups did not differ with regard to postoperative pain, bleeding, urine output, fever, length of paralytic ileus, or length of hospitalization. No major cardiovascular, pulmonary, or neurologic complications occurred in any of the patients either perioperatively or in the first 3 months postoperatively. CONCLUSIONS: Intraoperative anesthetic technique was not associated with a different postoperative complication rate in patients undergoing RRP. The very low incidence of complications and the uniform postoperative analgesic regimen may have contributed to the similarity between groups.

Analgesia, Patient-Controlled↗
PubMed1994

The effect of epidural versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing radical prostatectomy.

BACKGROUND: Although preemptive analgesia has been shown to decrease postinjury pain in animals, studies in humans have provided controversial results. The authors studied whether surgical epidural anesthesia with local anesthetics could affect postoperative pain and analgesic demands, when compared with general anesthesia. METHODS: Male patients scheduled for radical retropubic prostatectomy were randomly assigned to receive epidural anesthesia only (EA, n = 34), combined epidural and general anesthesia (EG, n = 32), or general anesthesia only (GA, n = 30). A lumbar epidural catheter was inserted and tested in all patients. In the EA group, an induction dose of 0.25 ml/kg epidural bupivacaine (0.5%) was followed during surgery by a continuous infusion of 0.1 ml.kg-1.h-1 0.125% bupivacaine. In the EG group, 0.2 ml/kg epidural bupivacaine (0.5%) was injected after induction of general anesthesia but before surgery, followed by epidural infusion of 0.1 ml.kg-1.h-1 0.125% bupivacaine. In the GA group, anesthesia was maintained with morphine, isoflurane, and N2O. Epidural patient-controlled analgesia (PCA) was provided with bupivacaine and fentanyl for all patients in the postoperative period. Postoperative pain scores and analgesic requirements were examined and compared between groups every 4-8 h for 3-5 postoperative days. RESULTS: Intraoperatively, EA patients received significantly more epidural bupivacaine than EG patients (129 +/- 6 mg vs. 98 +/- 6 mg, respectively. Recovery room median residual sensory level in EA patients (T6 +/- 2) was significantly higher than in EG patients (T10 +/- 2). PCA demand was greater in the GA and EG groups when compared with the EA group in postoperative days 2 (126 +/- 9 ml, 112 +/- 9 ml, 90 +/- 6 ml, respectively; P = 0.01) and 3 (89 +/- 10 ml, 83 +/- 9 ml, 48 +/- 5 respectively; P = 0.005). There was no difference in PCA demand between the GA and EG groups in the postoperative period. No significant clinical differences in postoperative mean pain scores were recorded in the first 5 days after surgery in the three anesthetic groups (range 0-2/10). CONCLUSIONS: In patients undergoing lower abdominal surgery, the neuraxial blockade and surgical anesthesia achieved by epidural local anesthetics was associated with decreased postoperative analgesic demands. Lower postoperative analgesic requirements in the EA group, when compared with both the EG and GA groups, indicate that: (1) EA patients had less postoperative pain, and (2) an efficient intraoperative blockade of noxious afferent signals to the central nervous system is fundamental in reducing postoperative pain.

Analgesia, Patient-Controlled↗