A reinvestigation of the analgesic effects induced by stimulation of the periaqueductal gray matter in the rat. I. The production of behavioral side effects together with analgesia

Fardin, V.; Olivéras, Jean-Louis; Besson, Jean‐Marie

doi:10.1016/0006-8993(84)90360-3

Cited by 227 publications

(64 citation statements)

References 77 publications

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“…Descending control originating in the PAG has been shown to powerfully modulate withdrawal reflexes evoked by noxious mechanical and thermal (heat) stimuli (e.g., Mayer et al, 1971;Fardin et al, 1984;Carstens et al, 1990;McMullan and Lumb, 2006a;Leith et al, 2007). However whether this control extends to noxious cold stimulation remains unclear; therefore, the effect of VL-PAG stimulation on cold-evoked withdrawal thresholds and response magnitudes was investigated.…”

Section: Cold-evoked Withdrawal Reflexes Are Significantly Depressed mentioning

confidence: 99%

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Leith¹,

Koutsikou²,

Lumb³

et al. 2010

J. Neurosci.

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In addition to cold being an important behavioral drive, altered cold sensation frequently accompanies pathological pain states. However, in contrast to peripheral mechanisms, central processing of cold sensory input has received relatively little attention. The present study characterized spinal responses to noxious and innocuous intensities of cold stimulation in vivo and established the extent to which they are modulated by descending control originating from the periaqueductal gray (PAG), a major determinant of acute and chronic pain. In lightly anesthetized rats, hindpaw cooling with ethyl chloride, but not acetone, was sufficiently noxious to evoke withdrawal reflexes, which were powerfully inhibited by ventrolateral (VL)-PAG stimulation. In a second series of experiments, subsets of spinal dorsal horn neurons were found to respond to innocuous and/or noxious cold. Descending control from the VL-PAG distinguished between activity in nociceptive versus non-nociceptive spinal circuits in that innocuous cold information transmitted by non-nociceptive class 1 and wide-dynamic-range class 2 neurons remained unaltered. In contrast, noxious cold information transmitted by class 2 neurons and all cold-evoked activity in nociceptive-specific class 3 neurons was significantly depressed. We therefore demonstrate that spinal responses to cold can be powerfully modulated by descending control systems originating in the PAG, and that this control selectively modulates transmission of noxious versus innocuous information. This has important implications for central processing of cold somatosensation and, given that chronic pain states are dependent on dynamic alterations in descending control, will help elucidate mechanisms underlying aberrant cold sensations that accompany pathological pain states.

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Section: Cold-evoked Withdrawal Reflexes Are Significantly Depressed mentioning

confidence: 99%

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Leith¹,

Koutsikou²,

Lumb³

et al. 2010

J. Neurosci.

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“…In addition, this region is a critical site for both stimulation-produced and morphine-induced analgesia (Reynolds, 1969;Behbehani and Fields, 1979;Fardin et al, 1984a;Fardin et al, 1984b;Morgan et al, 1991;Morgan et al, 1992;Zhang et al, 1998). Given that morphine produces a greater degree of analgesia in males in comparison to females (Cicero et al, 1996;Craft et al, 1996;Bartok and Craft, 1997;Cicero et al, 1997;Boyer et al, 1998;Tershner et al, 2000;Barrett et al, 2001;Cepeda and Carr, 2003;Stoffel et al, 2003;Stoffel et al, 2005;Wang and Murphy, 2005) and the PAG-RVM pathway is a critical circuit for opioid analgesia, we had initially hypothesized that if this circuit was sexually dimorphic, retrograde labeling from the RVM would be more prominent in males in comparison to females.…”

Section: Sexually Dimorphic Pag-rvm Circuit: Functional Implicationsmentioning

confidence: 99%

Sex differences in the anatomical and functional organization of the periaqueductal gray‐rostral ventromedial medullary pathway in the rat: A potential circuit mediating the sexually dimorphic actions of morphine

Loyd

Murphy

2006

J of Comparative Neurology

110

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Previous studies have demonstrated that morphine, administered systemically or directly into the PAG, produces a significantly greater degree of antinociception in males in comparison to females. As the midbrain periaqueductal gray (PAG) and its descending projections to the rostral ventromedial medulla (RVM) constitute an essential neural circuit for opioid-based analgesia, the present studies were conducted to determine if sex differences in the anatomical organization of the PAG-RVM pathway, and its activation during persistent inflammatory pain, could account for sex-based differences in opioid analgesia. In the rat, retrograde tracing was combined with Fos immunocytochemistry to investigate sexual dimorphism in the organization of the PAG-RVM circuit and its activation by persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA). The ability of morphine to suppress the activation of the PAG-RVM circuit was also examined. Sexually dimorphic retrograde labeling was observed within the dorsomedial and lateral/ventrolateral PAG at all rostrocaudal levels, with females having significantly more PAG-RVM output neurons in comparison to males. While no sex differences were noted in the activation of the PAG-RVM circuit by persistent inflammatory pain, significantly more double labeled cells were found in males in comparison to females. Systemic administration of morphine significantly suppressed CFA-induced Fos in the PAG in males only. The results of these studies demonstrate that both the anatomical organization, and functional activation, of the PAG-RVM circuit is sexually dimorphic, and may provide the anatomical substrate for sex-based differences in morphine analgesia.

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“…Thus, stimulation of the dorsal raphe potentiates, whereas its lesion blocks, morphine-induced analgesia (35). In fact, similarly to the ventrolateral PAG, the dorsal raphe has also been regarded as a purely analgesic region, and stimulation of this area elicits potent analgesia without aversive behavioral side effects (36).…”

Section: Specific Effect Of Stimulation At Point 36smentioning

confidence: 99%

c-Fos expression induced by electroacupuncture at the Zusanli point in rats submitted to repeated immobilization

Medeiros

Canteras

Suchecki

et al. 2003

Braz J Med Biol Res

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In laboratory animals, acupuncture needs to be performed on either anesthetized or, if unanesthetized, restrained subjects. Both procedures up-regulate c-Fos expression in several areas of the central nervous system, representing therefore a major pitfall for the assessment of c-Fos expression induced by electroacupuncture. Thus, in order to reduce the effect of acute restraint we used a protocol of repeated restraint for the assessment of the brain areas activated by electroacupuncture in adult male Wistar rats weighing 180-230 g. Repeated immobilization protocols (6 days, 1 h/day and 13 days, 2 h/ day) were used to reduce the effect of acute immobilization stress on the c-Fos expression induced by electroacupuncture at the Zusanli point (EA36S). Animals submitted to immobilization alone or to electroacupuncture (100 Hz, 2-4 V, faradic wave) in a non-point region were compared to animals submitted to electroacupuncture at EA36S (4 animals/subgroup). c-Fos expression was measured in 41 brain areas by simple counting of cells and the results are reported as number of c-Fos-immunoreactive cells/10,000 µm 2 . The protocols of repeated immobilization significantly reduced the immobilizationinduced c-Fos expression in most of the brain areas analyzed (P < 0.05). Animals of the EA36S groups had significantly higher levels of c-Fos expression in the dorsal raphe nucleus, locus coeruleus, posterior hypothalamus and central medial nucleus of the thalamus. Furthermore, the repeated immobilization protocols intensified the differences between the effects of 36S and non-point stimulation in the dorsal raphe nucleus (P < 0.05). These data suggest that high levels of stress can interact with and mask the evaluation of specific effects of acupuncture in unanesthetized animals.

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A reinvestigation of the analgesic effects induced by stimulation of the periaqueductal gray matter in the rat. I. The production of behavioral side effects together with analgesia

Cited by 227 publications

References 77 publications

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

Sex differences in the anatomical and functional organization of the periaqueductal gray‐rostral ventromedial medullary pathway in the rat: A potential circuit mediating the sexually dimorphic actions of morphine

c-Fos expression induced by electroacupuncture at the Zusanli point in rats submitted to repeated immobilization

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