Descending modulation from the region of the locus coeruleus on nociceptive sensitivity in a rat model of inflammatory hyperalgesia

Tsuruoka, Masayoshi; Willis, William D.

doi:10.1016/s0006-8993(96)01025-6

Cited by 60 publications

(31 citation statements)

References 36 publications

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“…Similar views have been advanced to account for the loss of spinal morphine suppression of somatic nociception and tactile allodynia following tight ligation of L5/L6 nerves. 24 There also is abundant evidence that descending inhibitory systems derived from either the rostroventral medulla (RVM) 11,32 or the locus coeruleus (LC) [33][34][35][36] are recruited following inflammation of somatic tissue. While these descending systems are present at birth, they are only partially functional by P10-P12 and become functionally mature by P21.…”

Section: Discussionmentioning

confidence: 99%

“…26 This enhanced bladder response was paralleled by a more global bladder hypersensitivity, manifested as increased micturition frequency 26 and decreased thresholds for micturition reflexes during cystometry. 8 Other studies of primary hyperalgesia and inflammation involving either the knee joint 31 or the hindpaw 28,39 have shown that descending inhibitory systems are progressively engaged during the first 24 hrs of acute inflammation and act to suppress somatic hyperalgesia (see also 11,27,[32][33][34][35][36] ). These data suggested the possibility that the urinary bladder hypersensitivity produced by acute bladder inflammation in the adult rat may be concomitantly suppressed by inflammation-induced activation of an inhibitory system 37,38 and that the enhancement effect we observed with neonatal exposure to zymosan might be due to impairment of this inhibitory system.…”

Section: Introductionmentioning

confidence: 99%

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Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

DeBerry

Ness

Robbins

et al. 2007

The Journal of Pain

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Abdominal electromyographic (EMG) responses to noxious intensities of urinary bladder distention (UBD) are significantly enhanced 24 hrs following zymosan-induced bladder inflammation in adult female rats. This inflammation-induced hypersensitivity is concomitantly inhibited by endogenous opioids because intraperitoneal (i.p.) naloxone administration before testing significantly increases EMG response magnitude to UBD. This inhibitory mechanism is not tonically active since naloxone does not alter EMG response magnitude to UBD in rats without inflammation. At the dose tested, naloxone does not affect bladder compliance in rats with or without inflammation. The effects of i.p. naloxone likely result from blockade of a spinal mechanism, because intrathecal (i.t.) naloxone also significantly enhances EMG responses to UBD in rats with inflammation. Rats exposed to bladder inflammation from P90-P92 prior to reinflammation at P120 show similar hypersensitivity and concomitant opioid inhibition, with response magnitudes being no different from that produced by inflammation at P120 alone. In contrast, rats exposed to bladder inflammation from P14-P16 prior to re-inflammation at P120 show markedly enhanced hypersensitivity and no evidence of concomitant opioid inhibition. These data indicate that bladder inflammation in adult rats induces bladder hypersensitivity that is inhibited by an endogenous opioidergic mechanism. This mechanism can be disrupted by neonatal bladder inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

DeBerry

Ness

Robbins

et al. 2007

The Journal of Pain

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“…A key finding is that in response to a persistent tissue injury, the activation of pain modulatory pathways is enhanced (Hurley and Hammond 2000;Kauppila et al 1998;Ren and Dubner 1996;Schaible et al 1991;Tsuruoka and Willis 1996;. The descending pathways also undergo time-dependent changes in excitability after injury.…”

Section: Introductionmentioning

confidence: 99%

Changes in Gene Expression and Neuronal Phenotype in Brain Stem Pain Modulatory Circuitry After Inflammation

Miki

Zhou

Guo

et al. 2002

Journal of Neurophysiology

132

102

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Changes in gene expression and neuronal phenotype in brain stem pain modulatory circuitry after inflammation. J Neurophysiol 87: 750 -760, 2002; 10.1152/jn.00534.2001. Recent studies indicate that descending pain modulatory pathways undergo time-dependent changes in excitability following inflammation involving both facilitation and inhibition. The cellular and molecular mechanisms of these phenomena are unclear. In the present study, we examined N-methyl-Daspartate (NMDA) receptor gene expression and neuronal activity in the rostral ventromedial medulla (RVM), a pivotal structure in pain modulatory circuitry, after complete Freund's adjuvant (CFA)-induced hindpaw inflammation. The reverse transcription polymerase chain reaction analysis indicated that there was an upregulation of mRNAs encoding NMDA receptor subunits in the RVM after inflammation. The increase in the NR1, NR2A, and NR2B receptor mRNAs started at 5 h, maintained for 1-7 days (P Ͻ 0.05-0.001) and returned to the control level at 14 days after inflammation. Western blot analysis indicated that the protein translation products of the NR2A subunit were also increased (P Ͻ 0.01). In single-unit extracellular recordings, we correlated RVM neuronal activity with the paw withdrawal response in rats with inflammation. We describe these RVM cells as on-, off-, and neutral-like cells because of their similarity to previous studies in which neuronal responses were correlated with tail-flick nocifensive behavior in the absence of inflammation. In contrast to previous studies in the absence of inflammation, using tail flick as a behavioral correlate, fewer off-like cells in naïve animals exhibited a complete pause before the paw withdrawal to a noxious thermal stimulus. The percentage of cells showing a pause of activity after noxious stimulation was further reduced after inflammation ( 2 P Ͻ 0.0001 vs. naïve rats). Continuous neuronal recordings (3-6.5 h) revealed a phenotypic switch of RVM neurons during the development of inflammation: 11/15 neutral-like cells initially unresponsive to noxious stimuli exhibited and maintained response profiles characteristic of pain modulatory neurons (became off-like: n ϭ 5; became on-like: n ϭ 6). Neutral-like cells recorded in noninflamed animals did not show response profile changes during continuous recordings (5-5.5 h, n ϭ 7). A population study (n ϭ 165) confirmed an increase in on-and off-like cells and a decrease in neutral-like cells at 24 h after inflammation as compared with naïve rats (P Ͻ 0.001). These results suggest that enhanced NMDA receptor activation mediates time-dependent changes in excitability of RVM pain modulatory circuitry. The functional phenotypic switch of RVM neurons provides a novel mechanism underlying activity-dependent plasticity and enhanced net descending inhibition after inflammation.

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“…More recently, peripheral inflammation has been recognized to also affect the efferent pain modulatory pathways. For example, persistent inflammatory injury can enhance either the inhibition or facilitation of spinal nociceptive transmission by medullary or pontine neurons (Schaible et al, 1991;Herrero and Cervero, 1996;Ren and Dubner, 1996;Tsuruoka and Willis, 1996;Urban et al, 1996Urban et al, , 1999Kauppila et al, 1998;Wei et al, 1998Wei et al, , 1999MacArthur et al, 1999;Terayama et al, 2000). Alterations in the activity of supraspinal neurons were inferred in most of these studies from lesion-induced changes in response latency or in the responses of the dorsal horn neurons to which these neurons project.…”

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confidence: 99%

Contribution of Endogenous Enkephalins to the Enhanced Analgesic Effects of Supraspinal μ Opioid Receptor Agonists after Inflammatory Injury

Hurley

Hammond

2001

J. Neurosci.

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This study examined a mechanism responsible for the enhanced antihyperalgesic and antinociceptive effects of the opioid receptor agonist (ORA) [D-Ala 2 , NMePhe 4 , Gly 5 -ol]enkephalin (DAMGO) microinjected in the rostroventromedial medulla (RVM) of rats with inflammatory injury induced by injection of complete Freund's adjuvant (CFA) in one hindpaw. In rats injected with CFA 4 hr earlier, microinjection of the opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-PenThr-NH 2 (CTAP) in the RVM antagonized both the marginal enhancement of the potency of DAMGO and its antinociceptive effect. The ␦ opioid receptor antagonist naltriben (NTB) was without effect. In rats injected with CFA 2 weeks earlier, CTAP antagonized the effects of DAMGO to a lesser extent. However, NTB completely prevented the enhancement of the potency of DAMGO, whereas it did not antagonize DAMGO's antinociceptive effects. Microinjection of NTB alone, but not CTAP in the RVM of CFA-treated rats, enhanced the hyperalgesia present in the ipsilateral hindpaw and induced hyperalgesia in the contralateral, uninjured hindpaw. These results suggest that persistent inflammatory injury increased the release in the RVM of opioid peptides with preferential affinity for the ␦ opioid receptor, which can interact in a synergistic or additive manner with an exogenously administered opioid receptor agonist. Indeed, the levels of [Met 5 ]enkephalin and [Leu 5 ]enkephalin were increased in the RVM and in other brainstem nuclei in CFAtreated rats. This increase most likely presents a compensatory neuronal response of the CNS of the injured animal to mitigate the full expression of inflammatory pain and to enhance the antinociceptive and antihyperalgesic effects of exogenously administered opioid receptor analgesics. Key words: opioid receptor; ␦ opioid receptor; antinociception; complete Freund's adjuvant; hyperalgesia; nucleus raphe magnusPeripheral inflammatory injury alters the pharmacology and physiology of primary afferent fibers that convey tactile and nociceptive information (Noguchi et al., 1988;Schaible and Schmidt, 1988;Donaldson et al., 1992;Ji et al., 1995;Leslie et al., 1995;Neumann et al., 1996;Tanaka et al., 1998), as well as the pharmacology and physiology of the dorsal horn neurons on which they synapse (Hylden et al., 1989;Noguchi et al., 1989;Weihe et al., 1989;McCarson and Krause, 1994;Goff et al., 1998). More recently, peripheral inflammation has been recognized to also affect the efferent pain modulatory pathways. For example, persistent inflammatory injury can enhance either the inhibition or facilitation of spinal nociceptive transmission by medullary or pontine neurons (Schaible et al., 1991;Herrero and Cervero, 1996;Ren and Dubner, 1996;Tsuruoka and Willis, 1996;Urban et al., 1996Urban et al., , 1999Kauppila et al., 1998;Wei et al., 1998Wei et al., , 1999MacArthur et al., 1999;Terayama et al., 2000). Alterations in the activity of supraspinal neurons were inferred in most of these studies from lesion-induced changes in response...

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Descending modulation from the region of the locus coeruleus on nociceptive sensitivity in a rat model of inflammatory hyperalgesia

Cited by 60 publications

References 36 publications

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

Changes in Gene Expression and Neuronal Phenotype in Brain Stem Pain Modulatory Circuitry After Inflammation

Contribution of Endogenous Enkephalins to the Enhanced Analgesic Effects of Supraspinal μ Opioid Receptor Agonists after Inflammatory Injury

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