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P N Fuchs

Publications and source records attributed to P N Fuchs.

25 records · Page 2Linked to original sources

Repeated cold water swim produces delayed nociceptive responses, but not analgesia, for tonic pain in the rat.

Earlier studies have demonstrated that cold water swim (CWS) produces stress-induced analgesia in tests of brief, phasic pain and produces a delayed nociceptive response (DNR) for more prolonged tonic pain. The present study reports the effect of repeated CWS on tonic pain, as measured by the formalin test. One group of rats was exposed to a 3.5-min swim in 2 degrees C water immediately prior to the formalin injection, to a 1.5-min swim at 50 min, and to another 1.5-min swim at 100 min postformalin injection. Compared to the no-swim control group, subjects which received repeated CWS had dramatically altered formalin pain responses. Formalin responses began just over 3 h postformalin injection, peaked at 4 h, and were still present at 5 h. Inspection of individual responses revealed a substantial degree of variability in the onset of responses, although the magnitude and duration of the formalin pain response remained at the same levels as those of control subjects. The lack of a decrease in the magnitude and duration of the delayed formalin responses indicates that repeated CWS does not produce analgesia for tonic pain. The period of stress, therefore, produces pain suppression but not loss of the mechanisms that subsequently underlie the pain. Earlier controls have ruled out peripheral mechanisms (such as retention of the formalin in the paw tissue). Rather, a memory mechanism appears to have been indicated and it is not lost, but persists until it can be manifested. Further research is needed to study the mechanisms responsible for the DNR.

Analgesia↗

Electrical stimulation of the cingulum bundle and surrounding cortical tissue reduces formalin-test pain in the rat.

Surgical lesions of the cingulum bundle in humans produce marked decreases in severe pain associated with cancer, reflex sympathetic dystrophy and other forms of chronic pain. Similarly, a temporary block of the anterior cingulum bundle in the rat by microinjection of lidocaine produces significant decreases in formalin-pain and reduces autotomy following peripheral neurectomy. The present study explored the effect of electrical stimulation of the cingulum bundle/surrounding cortical tissue (CB/CT) on tonic pain in the rat. Experiment 1 examined changes in formalin-induced pain responses following a 2.5-min period (30 s/min for 5 min) of electrical stimulation of the CB/CT 15 min prior to the formalin injection. The stimulation produced a significant reduction of first-period and second-period pain responses. Experiment 2 examined changes in formalin-induced pain responses following a 2.5-min period (30 s/min for 5 min) of electrical stimulation of the CB/CT 20 min following the formalin injection. The stimulation produced a dramatic reduction in second-period pain responses which persisted for the duration of the 35-min post-stimulation test period. The fact that either electrical stimulation or surgical section of the CB/CT produces pain relief suggests that this region serves a complex role in pain processing. Since the cingulum bundle has major connections with all other structures of the limbic system, it is possible that electrical stimulation disrupts patterned activity in the system, which is known to play an especially important role in the affective-motivational dimension of pain.

Animals↗

Delayed nociceptive response following cold-water swim in the formalin test: possible mechanisms of action.

Exposure of animals to aversive events produces stress-induced analgesia. A common method of producing stress in animals is the cold-water swim (CWS). The present series of experiments examines the effect of CWS on tonic pain, as measured by the formalin test, and explores possible mechanisms of action. Experiment 1 demonstrates that a 3.5-min swim in 2 degrees C water produces a delayed nociceptive response (DNR), characterized by a prolonged period of no formalin responding which then begins and continues during the time when control animals, which have not received the CWS, are finished responding. The delayed response begins at 50-60 min postformalin injection, peaks at 80 min, and is still present at 120 min. Experiment 2 indicates that paw temperature effects are not responsible for the DNR, although core body temperature effects are a possible mechanism. However, systematic delays in the formalin injection following the CWS (Experiment 3) drastically altered the DNR even though core body temperature remained unchanged, suggesting that a decrease of core body temperature is insufficient to account for the DNR. Experiment 4 demonstrates that the NMDA antagonist MK-801 administered prior to the CWS dramatically reduces the DNR. The present experiment is the first study that reports a delay as long as 60 min in pain responding. It is concluded that the delayed response to formalin injection is the result of complex interactions involving peripheral mechanisms and central neuronal plasticity in which activity initiated by a noxious input persists after the cessation of the input as a consequence of a stressful event such as the cold-water swim.

Animals↗

Restraint reduces formalin-test pain but the effect is not influenced by lesions of the hypothalamic paraventricular nucleus.

Previous research indicates that the paraventricular nucleus of the hypothalamus (PVN) plays an important role in the development of stress-induced analgesia (SIA). Research implicating the PVN in SIA has generally employed the cold-water swim as the stressor and a phasic pain test, such as the tail-flick test, as the pain model. The present study, using the formalin test for tonic pain, investigated the effect of PVN lesions on (1) tonic pain responses and (2) SIA caused by 30 min of restraint. Male Long-Evans rats were randomly assigned to one of four groups. Two groups received electrolytic lesions of the PVN and two additional groups served as sham-operated controls. One group which received PVN lesions and one group which was sham-operated were exposed to 30 min of restraint immediately prior to a 0.05-ml injection of 2.5% formalin into the planter surface of one hindpaw. The remaining groups which either received PVN lesions or were sham-operated received the formalin injection without prior exposure to restraint. During the first phase of the formalin response, PVN lesions did not alter duration of paw elevation scores, but significantly increased duration of paw licking scores. A 30-min period of restraint had no effect on duration of paw elevation scores, but significantly decreased duration of paw licking scores. PVN lesions did not alter the significant decrease in paw licking scores as a result of restraint. During the second phase of the formalin response, PVN lesions did not alter either the duration of paw elevation scores or the duration of paw licking scores. A 30-min period of restraint significantly decreased duration of paw elevation scores, but had no effect on duration of paw licking scores. PVN lesions did not alter the significant decrease in paw elevation scores as a result of restraint. The results indicate that PVN lesions increase paw licking only during the first phase of the formalin response, with no other alterations in paw licking or duration of paw elevation. In addition, a 30-min period of restraint can produce short-term and long-term SIA for tonic pain. The short-term SIA is reflected as a decrease in paw licking, whereas the long-term SIA is reflected as a decrease in paw elevation. In addition, PVN lesions failed to alter SIA during both phases of the formalin test. The differential effect of restraint on pain responses during the two phases of the formalin test and the lack of effect of PVN lesions on SIA for tonic pain suggest that stress engages multiple endogenous pain inhibitory systems.

Analgesia↗

Positive intrasurgical suggestion fails to affect postsurgical pain.

The present study explored the effect of positive intrasurgical suggestion during the anesthetic state on postsurgical pain. One-half of the patients who were undergoing elective cholecystectomy or hysterectomy received strong positive intrasurgical suggestion directed specifically towards reducing pain. The control patients received information about pain without suggestion content. There was no effect on postsurgical pain measured by the McGill Pain Questionnaire and a visual analogue scale. The lack of effect on postsurgical pain indicates that intrasurgical suggestion does not provide a therapeutic method to achieve pain control.

Adult↗

Analgesia induced by morphine microinjection into the lateral hypothalamus of the rat.

Earlier studies have demonstrated that electrical stimulation of the lateral hypothalamus (LH) produces analgesia in tests of brief, phasic pain and more prolonged tonic pain. The present experiment examined the effect of morphine microinjection into the LH on formalin-induced pain. The results show that a 10-micrograms morphine microinjection significantly decreases pain responses. Moreover, the decrease persists for the duration of the 25-min test period, which began 25 min after the formalin injection. These findings suggest that electrical stimulation of the LH engages an endogenous opiate system which is capable of producing prolonged analgesia.

Analgesia↗

Hypophysectomy produces analgesia and paraventricular lesions have no effect on formalin-induced pain.

Chemical destruction of the pituitary gland has been shown to alleviate severe cancer pain in a substantial proportion of patients. The underlying mechanisms, however, remain controversial. The present study investigated the effects of hypophysectomy in the formalin test, which provides an animal model of tonic pain, and attempted to determine a possible neural mechanism to explain the effectiveness of the procedure. Hypophysectomized rats displayed significantly less pain behavior in the formalin test than control rats that underwent a sham hypophysectomy, implicating the pituitary gland in the modulation of tonic pain. Since the paraventricular nucleus of the hypothalamus (PVN) provides a major source of input to the pituitary gland, the effects of electrolytic lesions of the PVN on tonic pain were examined. The results failed to show a significant effect of PVN lesions on pain responses in the formalin test. The results suggest that the pituitary gland modulates tonic pain in the formalin test and that the test provides an animal model to study possible mechanisms which underlie the relief of severe cancer pain by hypophysectomy. However, since PVN lesions did not affect the response of rats in the formalin test, it is possible that the PVN is only one of multiple interacting neural and endocrine structures that influence the functions of the pituitary.

Analgesia↗