Characterization of the antiallodynic efficacy of morphine in a model of neuropathic pain in rats

Bian, Di; Nichols, Michael L.; Ossipov, Michael H.; Lai, Josephine; Porreca, Frank

doi:10.1097/00001756-199510010-00007

Cited by 168 publications

(83 citation statements)

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“…Indeed, it has been shown that opioid receptors are mainly located on thin primary afferent fibers (Lamotte et al, 1976;Besse et al, 1990) and that morphine can block C and A␦ but not A␤ fiber-evoked responses into the dorsal horn (Le Bars et al, 1976;Dickenson and Sullivan, 1986;Sorkin andPuig, 1996, Dallel et al, 1998). Other studies have shown that thermal hyperalgesia and static allodynia induced by nerve injury are sensitive to systemic morphine, while the accompanying dynamic allodynia is resistant to morphine (Bian et al, 1995;Lee et al, 1995;Field et al, 1999a;Gonzalez et al, 2000;Catheline et al, 2001). The inefficiency of morphine on dynamic mechanical allodynia could be explained by the fact that pain results from pathways where opioid receptors do not control activity (Dickenson and Kieffer, 2006).…”

Section: Discussionmentioning

confidence: 99%

Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia

Miraucourt¹,

Moisset²,

Dallel³

et al. 2009

J. Neurosci.

118

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Dynamic mechanical allodynia is a widespread and intractable symptom of neuropathic pain for which there is a lack of effective therapy. We recently provided a novel perspective on the mechanisms of this symptom by showing that a simple switch in trigeminal glycine synaptic inhibition can turn touch into pain by unmasking innocuous input to superficial dorsal horn nociceptive specific neurons through a local excitatory, NMDA-dependent neural circuit involving neurons expressing the gamma isoform of protein kinase C. Here, we further investigated the clinical relevance and processing of glycine disinhibition. First, we showed that glycine disinhibition with strychnine selectively induced dynamic but not static mechanical allodynia. The induced allodynia was resistant to morphine. Second, morphine did not prevent the activation of the neural circuit underlying allodynia as shown by study of Fos expression and extracellularsignal regulated kinase phosphorylation in dorsal horn neurons. Third, in contrast to intradermal capsaicin injections, light, dynamic mechanical stimuli applied under disinhibition did not produce neurokinin 1 (NK1) receptor internalization in dorsal horn neurons. Finally, light, dynamic mechanical stimuli applied under disinhibition induced Fos expression only in neurons that did not express NK1 receptor. To summarize, the selectivity and morphine resistance of the glycine-disinhibition paradigm adequately reflect the clinical characteristics of dynamic mechanical allodynia. The present findings thus reveal the involvement of a selective dorsal horn circuit in dynamic mechanical allodynia, which operates through superficial lamina nociceptive-specific neurons that do not bear NK1 receptor and provide an explanation for the differences in the pharmacological sensitivity of neuropathic pain symptoms.

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Section: Discussionmentioning

confidence: 99%

Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia

Miraucourt¹,

Moisset²,

Dallel³

et al. 2009

J. Neurosci.

118

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“…Differential nerve blocks applied to patients demonstrated that allodynia is mediated through non-nociceptive, large diameter Aβ fibers whereas thermal hyperalgesia is mediated through the unmyelinated C-fiber nociceptors (Campbell et al 1988;Koltzenburg et al 1992;Koltzenburg et al 1994). Selective desensitization of Cfibers or presynaptic inhibition of C-fiber output with spinal morphine abolished thermal, but not tactile, hyperesthesias in rats with spinal nerve ligation (SNL) (Bian et al 1995;Lee et al 1995;Ossipov et al 1999). Likewise, inhibition of C-fiber activity did not alter behavioral responses to light brush in nerve-injured rats (Field et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Nerve injury-induced tactile allodynia is present in the absence of FOS labeling in retrogradely labeled post-synaptic dorsal column neurons

Zhang

Ossipov

Zhang

et al. 2007

Pain

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The dorsal column pathway consists of direct projections from primary afferents and of ascending fibers of the post-synaptic dorsal column (PSDC) cells. This pathway mediates touch but may also mediate allodynia after nerve injury. The role of PSDC neurons in nerve injury-induced mechanical allodynia is unknown. Repetitive gentle, tactile stimulus or noxious pinch was applied to the ipsilateral hindpaw of rats with spinal nerve ligation (SNL) or sham surgery that had previously received tetramethylrhodamine dextran in the ipsilateral n. gracilis. Both touch and noxious stimuli produced marked increases in FOS expression in other cells throughout all laminae of the ipsilateral dorsal horn after nerve injury. However, virtually none of the identified PSDC cells expressed FOS immunofluorescence in response to repetitive touch or pinch in either the nerve-injured or sham groups. In contrast, labeled PSDC cells expressed FOS in response to ureter ligation and labeled spinothalamic tract (STT) cells expressed FOS in response to noxious pinch. Identified PSDC neurons from either sham-operated or SNL rats did not express immunoreactivity to substance P, CGRP, NPY, PKCg, MOR, the NK1 and the NPY-Y1 receptor. Retrogradely labeled DRG cells of nerve injured rats were large diameter neurons, which expressed NPY, but no detectable CGRP or substance P. Spinal nerve injury sensitizes neurons in the spinal dorsal horn to repetitive light touch but PSDC neurons apparently do not participate in touch-evoked allodynia. Sensitization of these non-PSDC neurons may result in activation of projections integral to the spinal/supraspinal processing of enhanced pain states and of descending facilitation, thus priming the central nervous system to interpret tactile stimuli as being aversive.

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“…[7][8][9] Mu-receptor opioid agonists have been shown to reduce pain in a number of preclinical neuropathic pain models. [10][11][12] In humans, several randomized controlled trials have demonstrated that opioids reduce pain intensity, [13][14][15] and furthermore, decrease neuropathic pain-related disability. 16 Despite evidence of safety and efficacy in acute and cancer pain, studies have shown that physician and patient concerns about addiction and other adverse effects continue to be, often unwarranted, barriers to pain management in these settings.…”

mentioning

confidence: 99%

Trends in opioid use for chronic neuropathic pain: a survey of patients pursuing enrollment in clinical trials

Gilron

Bailey

2003

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : Clinical trials suggest that opioids relieve neuropathic pain and decrease pain-related disability. We conducted a pilot study of current prescribing trends and patients' attitudes towards opioids for neuropathic pain.M Me et th ho od ds s: : A patient questionnaire was completed by individuals pursuing enrollment in neuropathic pain clinical trials at our facility.R Re es su ul lt ts s: : Of 154 patients with diabetic neuropathy (55.2%), postherpetic neuralgia (29.9%), idiopathic peripheral neuropathy (9.7%) and other neuropathies (5.2%), 73.4% complained of inadequate pain control, the mean pain duration was 4.7 (SD = 4.4) yr and the mean pain intensity (0-10) was 7.7 (SD = 2.3). In this group, 40.9% had never tried opioids and 24.7% had never tried any opioids, tricyclic antidepressants or anticonvulsants. Only 9.7% were receiving long-acting opioids or "around the clock" dosing whereas 25.3% were receiving opioids on an "as needed" basis. Opioids combined with tricyclic antidepressants and/or anticonvulsants were used in 11.0%. Fear of addiction and adverse effects were expressed by 31.8% and 46.8% respectively.

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Characterization of the antiallodynic efficacy of morphine in a model of neuropathic pain in rats

Cited by 168 publications

References 0 publications

Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia

Glycine Inhibitory Dysfunction Induces a Selectively Dynamic, Morphine-Resistant, and Neurokinin 1 Receptor- Independent Mechanical Allodynia

Nerve injury-induced tactile allodynia is present in the absence of FOS labeling in retrogradely labeled post-synaptic dorsal column neurons

Trends in opioid use for chronic neuropathic pain: a survey of patients pursuing enrollment in clinical trials

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