Activity of medullary serotonergic neurons in freely moving animals

Jacobs, Barry L.; Martín-Cora, Francisco; Fornal, Casimir A.

doi:10.1016/s0165-0173(02)00187-x

Cited by 249 publications

(202 citation statements)

References 30 publications

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“…Serotonergic neurons in the nucleus raphe obscurus and pallidus in the medulla are implicated in fatigue since there is a strong correlation between neuronal activity and motor activity. 19 Both the nucleus raphe obscurus and pallidus, in addition to the nucleus raphe magnus, have also been shown to facilitate nociception 61 specifically in this muscle-induced model of hyperalgesia. 51 …”

Section: Central Mechanisms For Enhanced Nociception After Fatiguementioning

confidence: 97%

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

Yokoyama

Lisi

Moore

et al. 2007

The Journal of Pain

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Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 µL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were run for 2 h/day for 2 days prior to the first injection and 2 h/day for 2 days prior to the second injection. Muscle lactate, pCO 2 , pO 2 , creatinine kinase, phosphate, and histology were examined after the fatigue task and compared to a control group. Grip force was significantly decreased after 2 h of running indicating fatigue. The fatigue task did not induce muscle damage as there was no difference in muscle lactate, pCO 2 , pO 2 , creatinine kinase, phosphate, or histology. The fatigue task altered the dose-response relationship to intramuscular acidic saline injections. Mechanical hyperalgesia was observed in both fatigue and control groups after intramuscular injection of pH 4.0, but only the fatigue group after injection of pH 5. Neither the fatigue nor the control group developed hyperalgesia in response to intramuscular injection of pH 6 or pH 7.2. In conclusion, fatigue modified the susceptibility of mice to acid injection of pH 5.0 to result in mechanical hyperalgesia after 2 injections of pH 5.0. The fatigue task did not produce measurable changes in the muscle tissue suggesting a central mechanism mediating the enhancement of hyperalgesia.Perspective-These data therefore show that muscle fatigue can enhance the likelihood that one develops pain to a mild insult. Clinically, this could relate to the development of pain from such conditions as repetitive strain injury, and may relate to the interrelationship between chronic pain and fatigue. KeywordsFatigue; exercise; acid; protons; low-pH saline Pain arising from musculoskeletal disorders is a major clinical problem globally, 58 and fibromyalgia affects 2% of population in the United States. 57 As high as 76% of people with chronic widespread musculoskeletal pain conditions, such as fibromyalgia and arthritis, also report fatigue. 26 Conversely, as high as 94% of people with chronic fatigue syndrome report musculoskeletal pain and approximately half of the population has chronic widespread musculoskeletal pain. 56,60 Pain is increased during and after exercise in people with fibromyalgia and chronic fatigue syndrome. 20,48,54,55 Similarly, muscle fatigue is increased in people with chronic fatigue syndrome. 3,10,23 To assess mechanisms of chronic widespread pain, we developed an animal model that mimics the clinical symptoms. Two injections of acidic saline (pH 4.0), 5 days apart, into 1 muscle results in bilateral long-lasting hyperalgesia of the paw, 41 muscle,59 and the viscera28 without muscle tissue damage.41 The intramuscular pH decreases to a p...

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Section: Central Mechanisms For Enhanced Nociception After Fatiguementioning

confidence: 97%

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

Yokoyama

Lisi

Moore

et al. 2007

The Journal of Pain

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Section: The Circadian Systemmentioning

confidence: 99%

“…Non-photic environmental cues including exercise, food availability, temperature and stress can also directly and/or indirectly entrain the SCN. The activity of SCN neurons is also modulated by serotoninergic pathways and melatonin (Moore et al, 1978; Bosler and Beaudet, 1985; MeyerBernstein and Morin, 1996;Jacobs et al, 2002;Moore and Speh, 2004;Wirz-Justice, 2006).The SCN signal is translated into hormonal and autonomic signals for peripheral organs through its major outputs (i) the paraventricular nucleus (PVN) of the hypothalamus; and (ii) the pineal gland, where melatonin is synthesized according to the length of the photophase. Melatonin is the biochemical transducer of photoperiodic information to all cells in the body (including SCN neurons), and changes in duration and amplitude of nocturnal secretion serves to signal seasonal variations of day/night cycle length (for review see Simonneaux and Ribelayga, 2003).…”

mentioning

confidence: 99%

Does the circadian system regulate lactation?

Plaut

Casey

2012

Animal

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Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/ clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the 'setting' of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition.Keywords: mammary, lactation, circadian rhythm, photoperiod, metabolism ImplicationsThe circadian system coordinates internal physiological processes in mammals and synchronizes these processes to the animal's environment. We review the literature and discuss recent findings from our laboratory and others that suggest the circadian system regulates lactation, including coordinating changes in the dam's physiology needed to initiate and maintain lactation and mediating the photoperiod effect on milk production. Identification of environmental and physiological inputs that affect genes that control circadian rhythms will enable development of approaches to alter gene expression to maximize production efficiency in farm animals. IntroductionNearly all physiological and behavioral functions of animals are rhythmic including secretion patterns of hormones, sleep-wake cycle, metabolism and core body temperature.A circadian rhythm is a roughly 24-h cycle in the biochemical, physiological or behaviora...

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“…Serotonergic neurons are heavily implicated in the regulation of sensory and motor output (Jacobs et al, 2002). It is therefore perhaps unsurprising that impulsive action is modulated by a neurotransmitter system involved in the regulation of locomotor activity.…”

Section: Introductionmentioning

confidence: 99%

Fractionating Impulsivity: Contrasting Effects of Central 5-HT Depletion on Different Measures of Impulsive Behavior

Winstanley

Dalley

Theobald

et al. 2004

Neuropsychopharmacol

347

280

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Reducing levels of 5-HT in the central nervous system has been associated with increases in impulsive behavior. However, the impulsivity construct describes a wide range of behaviors, including the inability to withhold a response, intolerance to delay of reward and perseveration of a nonrewarded response. Although these behaviors are generally studied using instrumental paradigms, impulsivity may also be reflected in simple Pavlovian tasks such as autoshaping and conditioned activity. This experiment aimed to characterize further the effects of central 5-HT depletion and to investigate whether different behavioral measures of impulsivity are inter-related, thus validating the construct. Rats received intracerebroventricular (ICV) infusions of vehicle (n ¼ 10) or the serotonergic neurotoxin 5,7-dihydroxytryptamine (n ¼ 12) which depleted forebrain 5-HT levels by about 90%. Lesioned animals showed significant increases in the speed and number of responses made in autoshaping, increased premature responding on a simple visual attentional task, enhanced expression of locomotor activity conditioned to food presentation, yet no change in impulsive choice was observed, as measured by a delay-discounting paradigm. Significant positive correlations were found between responses made in autoshaping and the level of conditioned activity, indicating a possible common basis for these behaviors, yet no correlations were found between other behavioral measures. These data strengthen and extend the hypothesis that 5-HT depletion increases certain types of impulsive responding. However, not all measures of impulsivity appear to be uniformly affected by 5-HT depletion, or correlate with each other, supporting the suggestion that impulsivity is not a unitary construct.

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Activity of medullary serotonergic neurons in freely moving animals

Cited by 249 publications

References 30 publications

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

Does the circadian system regulate lactation?

Fractionating Impulsivity: Contrasting Effects of Central 5-HT Depletion on Different Measures of Impulsive Behavior

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