Sensitization of Pain Pathways in the Spinal Cord: Cellular Mechanisms

Baranauskas, Gytis; Nistri, Andrea

doi:10.1016/s0301-0082(97)00067-1

Cited by 275 publications

(151 citation statements)

References 120 publications

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“…The resolution of these questions will require spinal electrophysiological recordings in Fmr1 KO mice. In addition to LTP and LTD, a shorter-term form of nociceptive sensitization, called wind-up, is normally expressed in the spinal cord and is characterized by a gradual increase in C-fiberevoked spike activity in dorsal horn neurons and their ascending fibers (Baranauskas and Nistri, 1998;Herrero et al, 2000). Our findings demonstrate a clear reduction of wind-up in ascending fibers of the contralateral VLF in Fmr1 KO mice compared with wild-type mice, which adds additional weight to the hypothesis that spinal nociceptive sensitization is decreased in Fmr1 KO mice.…”

Section: Discussionmentioning

confidence: 99%

Decreased Nociceptive Sensitization in Mice Lacking the Fragile X Mental Retardation Protein: Role of mGluR1/5 and mTOR

Price¹,

Rashid²,

Millecamps³

et al. 2007

J. Neurosci.

187

245

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Fragile X mental retardation is caused by silencing of the gene (FMR1) that encodes the RNA-binding protein (FMRP) that influences translation in neurons. A prominent feature of the human disorder is self-injurious behavior, suggesting an abnormality in pain processing. Moreover, FMRP regulates group I metabotropic glutamate receptor (mGluR1/5)-dependent plasticity, which is known to contribute to nociceptive sensitization. We demonstrate here, using the Fmr1 knock-out (KO) mouse, that FMRP plays an important role in pain processing because Fmr1 KO mice showed (1) decreased (ϳ50%) responses to ongoing nociception (phase 2, formalin test), (2) a 3 week delay in the development of peripheral nerve injury-induced allodynia, and (3) a near absence of wind-up responses in ascending sensory fibers after repetitive C-fiber stimulation. We provide evidence that the behavioral deficits are related to a mGluR1/5-and mammalian target of rapamycin (mTOR)-mediated mechanism because (1) spinal mGluR5 antagonism failed to inhibit the second phase of the formalin test, and we observed a marked reduction in nociceptive response to an intrathecal injection of an mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) in Fmr1 KO mice; (2) peripheral DHPG injection had no effect in KO mice yet evoked thermal hyperalgesia in wild types; and (3) the mTOR inhibitor rapamycin inhibited formalin-and DHPG-induced nociception in wild-type but not Fmr1 KO mice. These experiments show that translation regulation via FMRP and mTOR is an important feature of nociceptive plasticity. These observations also support the hypothesis that the persistence of self-injurious behavior observed in fragile X mental retardation patients could be related to deficits in nociceptive sensitization.

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Section: Discussionmentioning

confidence: 99%

Decreased Nociceptive Sensitization in Mice Lacking the Fragile X Mental Retardation Protein: Role of mGluR1/5 and mTOR

Price¹,

Rashid²,

Millecamps³

et al. 2007

J. Neurosci.

187

245

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“…Limb withdrawal from mechanical stimulation can be elicited after spinal transection, suggesting that the change in tactile reactivity reported above could involve an intraspinal modification related to the sensitization of spinal neurons [30,31,32]. Vocalization to shock provides a supraspinal measure of sensory function and it revealed a different pattern of results; both prior shock and morphine treatment increased vocalization thresholds, suggesting both treatments increased the loss of sensory fibers.…”

Section: Methodsmentioning

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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“…Repeated or prolonged noxious stimulation may lead to sensitization which in turn can manifest clinically the phenomenon of allodynia [11], through altered functions of chemical, electrophysiological, and pharmacological systems [12]. A variety of painful conditions involve diffuse changes in the function of the nociceptive nervous system and, for this reason, fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome and endometriosis have all been linked to central sensitization [8] as well as to migraine [13].…”

Section: Introductionmentioning

confidence: 99%

Sensitization and pain

et al. 2013

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Migraine is often accompanied with signs of increased intracranial and extracranial mechanical sensitivities. The prevailing view today is that migraine headache is a neurovascular disorder with intracranial origin and involvement of meningeal blood vessels and their pain nerve fibers. Allodynia, defined as perception of pain following not painful stimulation, is a common clinical feature in various pain syndromes, and as part of migraine pain, it can be considered an indicator of trigeminal neural network sensitization. The cutaneous allodynia that accompanies the migraine headache in a large percentage of patients may be considered the clinical expression of central nervous system sensitization and is characterized by pain provoked by stimulation of the skin that would ordinarily not produce pain. An altered codification process of sensory impulses in the brainstem, in particular by the nucleus caudalis trigeminalis, may justify the temporal aspects and symptoms in the course of migraine attack.

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Sensitization of Pain Pathways in the Spinal Cord: Cellular Mechanisms

Cited by 275 publications

References 120 publications

Decreased Nociceptive Sensitization in Mice Lacking the Fragile X Mental Retardation Protein: Role of mGluR1/5 and mTOR

Decreased Nociceptive Sensitization in Mice Lacking the Fragile X Mental Retardation Protein: Role of mGluR1/5 and mTOR

The impact of morphine after a spinal cord injury

Sensitization and pain

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