Central sensitization and LTP: do pain and memory share similar mechanisms?

Ji, Ru-Rong; Kohno, Tatsuro; Moore, Kimberly A.; Woolf, Clifford J.

doi:10.1016/j.tins.2003.09.017

Cited by 1,252 publications

(1,037 citation statements)

References 106 publications

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“…Central sensitization has long been considered as a critical mechanism in chronic pain, and LTP is the cellular basis of memory. Ji found astonishing similarities between central sensitization and LTP after comparing the production and sustaining of them, particularly in the regulations and transportations of NMDARs and AMPARs (Ji, Kohno, Moore, & Woolf, 2003). Among the over 100 kinds of LTP‐related factors, many of them participate in spinal central sensitization and lead to hyperalgesia.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

Chen

Tang

et al. 2017

Brain and Behavior

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ObjectiveThe roles of hippocampal AMPARs were investigated in irritable bowel syndrome (IBS)‐like rats to clarify the central sensitization mechanisms.Methods IBS model was induced by neonatal maternal separation. The effects of AMPARs on visceral hypersensitivity were examined by the responses of abdominal muscle to colorectal distension after the bilateral intrahippocampal injections of CNQX (an AMPAR inhibitor). The expressions of hippocampal AMPARs (GluR1 and GluR2) were determined by Western blot.ResultsThe IBS‐like rats showed visceral hypersensitivity when compared with controls. Bilateral intrahippocampal injections of CNQX alleviated the visceral pain in IBS‐like rats. The maximal effect appeared at the time point of 30 min, and the duration lasted for 90 min after CNQX application, under 40 and 60 mmHg CRD. The expressions of hippocampal GluR2 significantly increased in IBS‐like rats when compared with controls (p < .05). However, the levels of hippocampal GluR1 had no significant differences in rats. Hippocampal LTP induced by HFS was significantly enhanced when compared with controls (p < .05). The expressions of GluR2 significantly increased in the control and IBS‐like rats after 60 min LTP of recordings (p < .05), but not GluR1.ConclusionNeonatal maternal separation enhances the expression of GluR2 and facilitates the LTP in the hippocampus, which could lead to the formation of visceral hypersensitivity when grown up.

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Section: Discussionmentioning

confidence: 99%

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

Chen

Tang

et al. 2017

Brain and Behavior

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“…Activity in pain (nociceptive) fibers after a spinal injury can provide an uncontrollable source of over-excitation [1,2,3], and can lead to maladaptive alterations within the central nervous system. This central excitability is derived not only from the spinal injury itself, but also from accompanying peripheral tissue damage.…”

Section: Introductionmentioning

confidence: 99%

The impact of morphine after a spinal cord injury

Hook

Liu

Washburn

et al. 2007

Behavioural Brain Research

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Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury.

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“…However, in the presence of nociceptive stimulation, the evidence reviewed above suggests that anesthesia can have an adverse effect by removing a form of negative feedback that normally suppresses the development of spinal central sensitization, a phenomenon that has been linked to both the development of neuropathic pain and the inhibition of adaptive plasticity (Woolf 1983;Treede et al 1992;Ferguson et al 2006). Central sensitization is thought to depend on a form of NMDAR-mediated plasticity and has been tied to the development of spinal longterm potentiation (LTP; Woolf and Thompson 1991;Ji et al 2003). Prior work indicates that the induction of spinal LTP is suppressed by descending inhibition (Sandkuhler and Liu 1998); therefore, any manipulation that interferes with this inhibition could foster the development of central sensitization.…”

Section: Discussionmentioning

confidence: 99%

“…These effects appear to be mediated by some of the same neurochemical mechanisms implicated in neurobiological models of learning and memory within the brain (Harris et al 1984;Morris et al 1986). For example, all depend on a form of NMDA-receptor (NMDAR)-mediated plasticity (Durkovic and Prokowich 1998;Ji et al 2003;Joynes et al 2004;Ferguson et al 2006;Woolf and Thompson 1991).…”

Section: Introductionmentioning

confidence: 99%

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

et al. 2007

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Rationale-Spinal cord plasticity can be assessed in spinal rats using an instrumental learning paradigm in which subjects learn an instrumental response, hindlimb flexion, to minimize shock exposure. Prior exposure to uncontrollable intermittent stimulation blocks learning in spinal rats but has no effect if given before spinal transection, suggesting that supraspinal systems modulate nociceptive input to the spinal cord, rendering it less susceptible to the detrimental consequences of uncontrollable stimulation.Objective-The present study examines whether disrupting brain function with pentobarbital blocks descending inhibitory systems that normally modulate nociceptive input, making the spinal cord more sensitive to the adverse effect of uncontrollable intermittent stimulation. Materials and methods-MaleSprague-Dawley rats received uncontrollable intermittent stimulation during pentobarbital anesthesia after (experiment 1) or before (experiment 2) spinal cord transection. They were then tested for instrumental learning at a later time point. Experiment 3 examined whether these manipulations affected nociceptive (thermal) thresholds.Results-Experiment 1 showed that pentobarbital had no effect on the induction of the learning deficit after spinal cord transection. Experiment 2 showed that intact rats anesthetized during uncontrollable intermittent stimulation failed to learn when later transected and tested for instrumental learning. Experiment 3 found that uncontrollable intermittent stimulation induced an antinociception in intact subjects that was blocked by pentobarbital. Conclusions-The results suggest a surgical dose of pentobarbital (50 mg/kg) suppresses supraspinal (experiment 2) but not spinal (experiment 1) systems that modulate nociceptive input to the spinal cord by blocking the antinociception that is induced by this input (experiment 3).

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Central sensitization and LTP: do pain and memory share similar mechanisms?

Cited by 1,252 publications

References 106 publications

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

The impact of morphine after a spinal cord injury

Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

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