Bi-directional changes in affective state elicited by manipulation of medullary pain-modulatory circuitry

Hirakawa, Naomi; Tershner, Sheralee A.; Fields, Howard L.; Manning, Barton H.

doi:10.1016/s0306-4522(00)00329-8

Cited by 37 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data indicate that F13640 both prevents and reverses morphineinduced CPP, suggesting this CPP to be mediated by opioid pain. Consistent with this, neuronal systems that have traditionally been associated with pain processing also mediate bidirectional affective states (Hirakawa et al, 2000;Laviolette et al, 2004).…”

Section: Discussionmentioning

confidence: 56%

“…In the rostral ventromedial medulla, ON, OFF and neutral cells projecting to the spinal and trigeminal dorsal horn modulate pain processing; manipulations of these neurons produce bidirectional, pro-and hypoalgesic actions the sensory and affective qualities of which seem to be closely matched (Hirakawa et al, 2000). Such modulation can be reinstated by re-exposure to the environment to which pain-induced aversion had previously been conditioned (Lei et al, 2004).…”

Section: -Htmentioning

confidence: 99%

See 1 more Smart Citation

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

Colpaert

Deseure²,

Stinus³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Pain may become intractable as tolerance develops to opioids and the opioids, paradoxically, induce pain. We examined the hypothesis that the analgesia produced by the novel analgesic and high-efficacy 5-hydroxytryptamine (5-HT) 1A receptor agonist (3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]methyl}piperidin-1-yl]methanone, fumaric acid salt (F 13640) may counteract opioid-induced pain. In studies of the somatosensory quality of pain in infraorbital nerve-injured rats, morphine infusion (5 mg/day) by means of osmotic pumps initially caused analgesia (i.e., decreased the behavioral response to von Frey filament stimulation), followed by hyperallodynia and analgesic tolerance. Infusion of F 13640 (0.63 mg/day) prevented the development of opioid hyperallodynia and reversed opioid hyperallodynia once established. In studies of the affective/motivational quality of pain, F 13640 both prevented and reversed the conditioned place aversion induced by naloxone (0.04 mg/kg i.p.) in morphine-infused rats; F 13640 also prevented and reversed the conditioned place preference induced by morphine injections (7.5 mg/kg i.p.). The data confirm that opioids produce bidirectional hypo-and proalgesic actions, and offer initial evidence that high-efficacy 5-HT 1A receptor activation counteracts both the sensory and the affective/motivational qualities of opioid-induced pain. The data also indicate that F 13640 may be effective with opioidresistant pain. It further is suggested that opioid addiction may represent self-therapy of opioid-induced pathological pain.Although opioids produce powerful pain relief, pain may become intractable as tolerance develops to opioid analgesia; it has been proposed that this is because opioids may, paradoxically, induce pain. Indeed, a concept of signal transduction in central pain-processing systems (Colpaert, 1996) specifies that any input to such systems causes not a single effect but two dual effects that are bidirectional, or opposite in sign. Thus, morphine eventually causes not only analgesia as a "first order" effect but also a "second order" hyperalgesia that outlasts opioid receptor activation for some time. Upon chronic opioid exposure, the second order pain, or sensitization to nociceptive input, grows and neutralizes the first order analgesia. Considerable evidence now indicates that tolerance to opioid analgesia results from opioid-induced pain ("opioid pain"; here used to refer to hyperalgesia, allodynia, and hyperallodynia; Colpaert, 1996;Mao, 2002;Ossipov et al., 2003).Opioid pain is comprehensive, encompassing both the "physiological" (e.g., nociceptive) and the more recently identified (Scholz and Woolf, 2002) "pathological" (e.g., neuropathic) types of pain. Indeed, opioids not only produce hyperalgesia (i.e., an enhanced response to nociceptive stimulation; Colpaert, 1996) but also neuropathic-like allodynia (i.e., pain behaviors in response to innocuous stimuli; Ossipov et al., 2003). In human, opioid pain occurs after the intraoperative ...

show abstract

Section: Discussionmentioning

confidence: 56%

Section: -Htmentioning

confidence: 99%

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

Colpaert

Deseure²,

Stinus³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…This is consistent with the fact that the LC possesses the greatest concentration of a 1 -receptors by far in the rodent dorsal pons (Jones et al, 1985;Stone et al, 2004a). However, this does not mean that a 1 -receptors in other brain regions are not involved in positive reinforcement; in fact, a 1 -agonists injected in the rostral ventrolateral medulla have been found to support CPP (Hirakawa et al, 2000).…”

Section: Discussionmentioning

confidence: 94%

Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle

Yang

Vaca

Stone

2006

Neuropsychopharmacol

View full text Add to dashboard Cite

The present experiments were undertaken to clarify the role of central a 1 -adrenoceptors in reward processes. Rats, trained to selfstimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered a 1 -selective drugs near the locus coeruleus (LC), a site of a dense concentration of a 1 -receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC a 1 -receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the a 1 -agonist, phenylephrine and were not attributable to terazosin's weak action at a 2 -adrenoceptors. It is concluded that LC a 1 -adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment. Neuropsychopharmacology (2007) 32, 835-841.

show abstract

“…Although Morgan and Whitney (2000) reported immobility in an open field with RVM stimulation, they characterized this as defensive freezing, since the animals were able to ambulate when handled. Finally, human patients that receive pain relief from stimulation of the periventricular gray report analgesia rather than motor inhibition (Hosobuchi et al, 1977, Barbaro, 1988, and activation of RVM neurons alters affective state as well as nociception (Hirakawa et al, 2000). Although the boundary between sensory and motor systems cannot be clearly demarcated, these data collectively indicate that RVM onand off-cells influence sensory processing.…”

Section: On-cell Burst and Off-cell Pause Are Reflex-relatedmentioning

confidence: 92%

Are opioid-sensitive neurons in the rostral ventromedial medulla inhibitory interneurons?

2008

View full text Add to dashboard Cite

mu-Opioid agonists frequently activate output neurons in the brain via disinhibition, that is, by inhibiting "secondary cells," which results in disinhibition of "primary cells," considered to be output neurons. Secondary cells are generally presumed to be inhibitory interneurons that serve only to regulate the activity of the output neurons. However, studies of the opioid-sensitive neurons in the rostral ventromedial medulla, a region with a well-documented role in nociceptive modulation, indicate that the opioid-inhibited neurons in this region (termed "on-cells" when recorded in vivo) have a distinct functional role that parallels and opposes the output of the subset of RVM neurons that are activated following opioid administration, the "off-cells." The aim of the present study was to analyze the relative timing of on- and off-cell reflex-related firing in the rostral ventromedial medulla to help determine whether on-cells are likely to function as inhibitory interneurons in this region. On- and off-cells display complementary firing patterns during noxious-evoked withdrawal: off-cells stop firing and on-cells show a burst of activity. If on-cells are inhibitory interneurons mediating the off-cell pause, the on-cells would be expected to begin their reflex-related discharge before the off-cells cease firing. To examine this we recorded activity of on- and off-cell pairs during heat-evoked paw or tail withdrawal in lightly anesthetized rats. For each cell pair, we measured the onsets of the off-cell pause and the on-cell burst. Contrary to what would be expected if on-cells were inhibitory interneurons, off-cells typically ceased firing before on-cells began reflex-related firing, with a mean 481 (+/-69) ms lag between the final off-cell spike and the first on-cell spike. This suggests that on-cells do not mediate the off-cell pause, and points instead to presynaptic mechanisms in opioid-mediated disinhibition of medullary output neurons. These data also support an independent role for on-cells in pain modulation.

show abstract

Bi-directional changes in affective state elicited by manipulation of medullary pain-modulatory circuitry

Cited by 37 publications

References 37 publications

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning

Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle

Are opioid-sensitive neurons in the rostral ventromedial medulla inhibitory interneurons?

Contact Info

Product

Resources

About