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L R Watkins

Publications and source records attributed to L R Watkins.

157 records · Page 9Linked to original sources
PubMed1982

Opiate vs non-opiate footshock induced analgesia (FSIA): descending and intraspinal components.

Opiate and non-opiate footshock induced analgesia (FSIA) can be differentially elicited dependent upon the body region shocked. As measured by the spinally-mediated tail flick test, hind paw shock produces non-opiate analgesia where front paw shock produces opiate analgesia. The present series of experiments utilized cord lesions and transections to identify descending and intraspinal pathways mediating front paw and hind paw FSIA. The results of these studies indicate that front paw shock leads to activation of supraspinal sites which mediate analgesia via descending pathways lying solely within the dorsolateral funiculus (DLF) of the spinal cord; direct intraspinal pathways are not involved. Hind paw FSIA is also mediated by a descending DLF pathway but is unlike front paw FSIA in that it involves intraspinal pathways as well. This work provides further parallels between the analgesias produced by morphine, electrical brain stimulation and environmental stimuli.

Analgesia↗
PubMed1982

Classical conditioning of front paw and hind paw footshock induced analgesia (FSIA): naloxone reversibility and descending pathways.

Opiate and non-opiate footshock induced analgesia (FSIA) has recently been observed to be differentially elicited dependent upon the body region shocked; front paw and hind paw shock produce opiate and non-opiate analgesia, respectively. Previous studies have shown that footshock can also produce classically conditioned analgesia; that is, when shock is delivered to an animal, environmental cues become associated with the noxious stimulus such that these cues become capable, in and of themselves, of producing potent analgesia. The present series of experiments examined analgesia classically conditioned to either front paw or hind paw shock. The non-electrified shock grid served as the conditioned stimulus (CS), 90-s footshock as the unconditioned stimulus (UCS) and tail-flick inhibition as the unconditioned response (UCR). Following CS-UCS pairings, exposure to the non-electrified grid reliably produced prolonged analgesia. This classically conditioned analgesia appears to involve endogenous opioids, regardless of the body region shocked during conditioning trials, since the analgesia is attenuated by systemic naloxone and shows cross-tolerance to morphine. A spinal opioid site is involved since 1 microgram of naloxone delivered directly to the lumbosacral cord antagonizes the analgesia. Like front paw (opiate) FSIA, CCA can be prevented but cannot be reversed by naloxone; naloxone can antagonize classically conditioned analgesia only if it is delivered prior to exposure to the conditioned stimulus. Lastly, a similarity was recognized between classically conditioned analgesia and the analgesia induced by morphine, brain stimulation, front paw shock and hind paw shock in that all are mediated via descending pathways within the dorsolateral funiculus of the spinal cord.

Analgesia↗
PubMed1982

Opiate vs non-opiate footshock-induced analgesia (FSIA): the body region shocked is a critical factor.

Previous work has demonstrated that footshock can elicit either opiate or non-opiate analgesia. The present study has demonstrated that one critical factor determining the involvement of endogenous opioids is the body region shocked. Using 90 s shock, front paw shock produced an opiate analgesia which was significantly antagonized by as little as 0.1 mg/kg systemic naloxone and morphine tolerance. In the latter experiment, a parallel recovery of the analgesic potencies of both front paw shock and morphine was observed following 2 weeks of opiate abstinence. In contrast, hind paw shock produced a non-opiate analgesia which failed to be attenuated by 20 mg/kg systemic naloxone and showed no cross-tolerance to morphine. Since identical shock parameters were used for front paw and hind paw shock in the systemic naloxone experiments, stress per se clearly cannot be the crucial factor determining the involvement of endogenous opioids in footshock-induced analgesia. These results were discussed with respect to clinical treatments of pain which utilize somatosensory stimulation.

Analgesia↗
PubMed1982

Involvement of spinal opioid systems in footshock-induced analgesia: antagonism by naloxone is possible only before induction of analgesia.

Footshock reliably produces analgesia in rats which is mediated either by opiate or non-opiate systems. It has recently been demonstrated that a critical factor determining the involvement of endogenous opioids is the body region shocked; front paw shock produces a naloxone-reversible analgesia and hind paw shock produces an analgesia which fails to be attenuated by this opiate antagonist. The present study demonstrated that a crucial opiate site for the production of front paw footshock-induced analgesia (FSIA) exists within the spinal cord. One microgram of naloxone delivered directly to the lumbosacral cord immediately prior to shock significantly attenuated this analgesia. However, the efficacy of naloxone antagonism was order-dependent in that naloxone failed to antagonize fron paw FSIA if delivered immediately after shock; naloxone could prevent but could not reverse the analgesic state. The body region shocked was again observed to be a critical factor determining the involvement of endogenous opioids since 1 microgram of spinal naloxone failed to antagonize hind paw FSIA. These results were discussed in light of recent evidence proposing a neuromodulatory role of opioids within the spinal cord.

Analgesia↗
PubMed1982

Organization of endogenous opiate and nonopiate pain control systems.

Research during the past decade has revealed the existence of neural systems that modulate pain transmission. Much of this work has focused on the role of endogenous opiate systems, but recent research indicates the involvement of nonopiate mechanisms as well. In this article, we present data demonstrating that opiate and nonopiate analgesia systems can be selectively activated by different environmental manipulations and describe the neural circuitry involved. Both neural and hormonal pathways and both opiate and nonopiate substances play roles in the complex modulation of pain transmission. The existence and description of these modulatory mechanisms have important clinical implications for the treatment of pain.

Acupuncture Therapy↗
PubMed1982

Failure of spinal cord serotonin depletion to alter analgesia elicited from the periaqueductal gray.

The effects of spinal cord serotonin depletion or combined serotonin/norepinephrine depletion on analgesia elicited by electrical stimulation of, or morphine microinjection into, the periaqueductal gray, were tested. Spinal cord serotonin was depleted by intrathecal injection of 5,7-dihydroxytryptamine (5,7-DHT), preceded by systemic desipramine, while 5,7-DHT alone was used to deplete both norepinephrine and serotonin. Selective serotonin depletion had no effect on analgesia induced by either method at 24 h, 1 week, or 2 weeks after treatment. Depletion of both monoamines had no effect on stimulation produced analgesia 24 h and one week after treatment, but produced a slight attenuation 2 and 3 weeks after treatment. In contrast, depletion of both monoamines drastically attenuated morphine analgesia 24 h after treatment. The results are discussed in relation to multiple pain inhibitory pathways.

5,7-Dihydroxytryptamine↗
PubMed1981

Identification and somatotopic organization of nuclei projecting via the dorsolateral funiculus in rats: a retrograde tracing study using HRP slow-release gels.

Horseradish peroxidase (HRP) in slow-release gel was unilaterally implanted in the transected dorsolateral funiculus (DLF) of either cervical, midthoracic, lumbar or sacral spinal cord levels of adult male rats. Cell mappings were made of all brain areas projecting through the DLF. Following cervical implants, dense labelling was observed within a band along the dorsolateral border of the inferior olive, locus coeruleus, the paralemniscal reticular formation, the mesencephalic central gray, the red nucleus and the paraventricular nucleus of the hypothalamus. The DLF projection from the central gray consisted of a rostrocaudal line of cells extending from the level of the mesen-/diencephalic junction to the rostral red nucleus. The somatotopic organization of labelled nuclei was assessed by comparing the pattern of filled cells following HRP implants at various cord levels. The potential role of these areas in pain modulation was discussed in light of their descending projections through the DLF of the spinal cord.

Afferent Pathways↗
PubMed1980

The somatotopic organization of the nucleus raphe magnus and surrounding brain stem structures as revealed by HRP slow-release gels.

Horseradish peroxidase (HRP) in slow-release gel was unilaterally implanted in the dorsal lateral funiculus (DLF) of either cervical, midthoracic, lumbar or sacral spinal cord levels of adult male rats. Complete mappings and cell counts were made of HRP-filled cells from the level of the rostral trapezoid body caudal to the inferior olive. Following cervical or midthoracic placements, labelled cells often formed a continuous band surrounding the medial, dorsal and lateral aspects of the ipsilateral pyramid and extending into the ventral region medial to the facial nucleus and lateral to the pyramid. It appears that this population of HRP-filled cells in the nucleus raphe magnus (NRM) and reticularis magnocellularis (Rmc) corresponds to the serotonergic cell group B3 of Dahlström and Fuxe. In lumbar and sacral cases, there was a noticeable difference both in the pattern and number of labelled cells, with fewer labelled cells and greater tendency for a 'gap' to occur in the population of cells midway over the pyramid. Based on the patterns of labelling and a review of the literature, its appears that the actual functional unit involved in the descending control of nociception may be the combined population of Rmc and NRM.

Animals↗
PubMedDate not supplied

Characterization of intrathecal vasopressin-induced antinociception, scratching behavior, and motor suppression.

Intrathecal (IT) administration of vasopressin produces antinociception, scratching behavior, and motor suppression. The present experiments characterized these effects with regards to the following: 1) VP receptor specificity, 2) possible involvement of endogenous opiates, 3) possible involvement of seizure activity, and 4) whether the antinociception is due to direct actions of VP at the spinal cord. These studies showed that IT administration of a V1-specific vasopressin antagonist completely blocked the antinociception, scratching behavior, and motor suppression produced by 25 ng IT vasopressin. Furthermore, IT administration of the vasopressin metabolite, [pGlu4,Cyt6]AVP(4-9), produced none of the effects produced by vasopressin. Systemic administration of the opiate antagonists naloxone (1 mg/kg IP) and naltrexone (10 mg/kg IP) had no significant effect on the antinociception produced by IT vasopressin, whereas naltrexone potentiated the scratching behavior. Neither the IT vasopressin-induced antinociception nor scratching behavior was affected by pretreatment with the anticonvulsant sodium valproate. In addition, IT vasopressin inhibited the tail flick reflex in rats with transected spinal cords, demonstrating direct spinal effects of vasopressin. In conclusion, IT administration of vasopressin produces antinociception, scratching behavior, and motor suppression via activation of VP-specific receptors in the spinal cord.

Animals↗
PubMedDate not supplied

Bacterial endotoxin induces fos immunoreactivity in primary afferent neurons of the vagus nerve.

Subdiaphragmatic vagotomy inhibits brain-mediated illness responses to peripherally administered bacterial endotoxin, including fever, hyperalgesia, sickness behavior, and activation of the hypothalamic-pituitary-adrenal axis. However, direct evidence implicating vagal afferents specifically in conveying information about peripheral immune activation to the brain is still lacking. This study assessed whether (1) endotoxin induces the expression of the functional activation marker Fos in the vagal sensory ganglia, and (2) vagotomy abrogates endotoxin-induced Fos expression in these ganglia. Male rats, which had previously received vagotomy or sham surgery, were injected intraperitoneally or intravenously with either endotoxin or saline. Fos immunolabeling was absent in saline-treated rats. In contrast, scattered cells within the vagal sensory ganglia showed Fos immunoreactivity after both intraperitoneal and intravenous endotoxin administration in sham-operated rats. Vagotomy abolished Fos expression after intraperitoneal endotoxin administration, whereas after intravenous administration Fos expression was strongly attenuated, but not eliminated. These findings implicate vagal afferents as a potential signaling pathway to brain regions that generate illness responses to pro-inflammatory mediators.

Animals↗
PubMedDate not supplied

Acute stress may facilitate recovery from a subcutaneous bacterial challenge.

The effects of stress on the immune system vary with both the duration and type of stressor. Many studies suggest that stress may compromise an organism's ability to recover from immune challenge. However, recent findings suggest that stress may actually enhance some aspects of immune function. For example, exposure to a single session ( approximately 2 h) of intermittent inescapable tailshocks (IS) has been shown to activate the acute phase response and increase some aspects of macrophage function. Thus, the following experiments assessed whether IS exposure would alter local inflammation produced by peripheral injection of streptomycin-killed bacteria. Rats (Harlan Sprague Dawley) were exposed to IS (100 1. 6-mA, 60 s variable intertrial interval) and injected with Escherichia coli ( approximately 2.5 x 10(8) CFU s.c. posterior to the shoulder blades). The area of inflammation was measured until the inflammation had completely resolved (typically 7-8 days). When bacteria were administered immediately after IS, rats resolved inflammation significantly faster than did nonstressed rats. Since adrenalectomy did not reduce the effect of IS, it is unlikely that this effect is a result of elevated corticosterone levels. Furthermore, IS does not appear to alter the rat's ability to sequester bacteria in the subcutaneous space since no swelling of lymph nodes or chronic activation of the hypothalamic-pituitary-adrenal axis was observed.

Animals↗