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R Dubner

Publications and source records attributed to R Dubner.

At least 37 records · Page 2Linked to original sources
PubMed1999

Medullary dorsal horn neuronal activity in rats with persistent temporomandibular joint and perioral inflammation.

Studies at spinal levels indicate that peripheral tissue or nerve injury induces a state of hyperexcitability of spinal dorsal horn neurons that participates in the development of persistent pain and hyperalgesia. It has not been demonstrated that persistent injury in the orofacial region leads to a similar state of central hyperexcitability in the trigeminal system. The purpose of the present study was to conduct a parametric analysis of the response properties of nociceptive and nonnociceptive neurons in trigeminal nucleus caudalis (medullary dorsal horn, MDH) in a rat model of persistent orofacial inflammation. Neurons were recorded extracellularly and classified as low-threshold mechanoreceptive (LTM, n = 49), wide dynamic range (WDR, n = 82), and nociceptive-specific (NS, n = 11) neurons according to their response properties to mechanical stimuli applied to their cutaneous receptive fields (RFs). The inflammation was induced 24 h before the recordings by injecting complete Freund's adjuvant (CFA) into the temporomandibular joint (TMJ) capsule or the perioral (PO) skin. The mean areas of the high-threshold RFs of WDR neurons in TMJ (8.66 +/- 0.61 cm(2), n = 25) and PO (5.61 +/- 2.07 cm(2), n = 25) inflamed rats were significantly larger than those in naive rats (1.10 +/- 0. 16 cm(2), n = 32). The mean RF size in TMJ-inflamed rats also was significantly larger than that in PO-inflamed rats (P < 0.01). Furthermore the mean area of the RFs of NS neurons (3.74 +/- 1.44 cm(2), n = 5) was significantly larger in TMJ inflamed rats as compared with naive rats (0.4 +/- 0.09 cm(2), n = 3) (P < 0.05). The background activity in the TMJ- and PO-inflamed rats was generally greater in WDR and NS neurons, but less in LTM neurons, when compared with naive rats. The responses of WDR neurons to noxious mechanical stimuli were increased significantly in TMJ-inflamed rats (P < 0.05) as compared with naive rats. WDR neuronal responses to mechanical stimulation also were increased in PO-inflamed rats but to a lesser extent than in TMJ-inflamed rats. The injection of CFA into the TMJ or PO skin resulted in reduced responses of LTM neurons to mechanical stimuli. The responses of MDH nociceptive neurons to 48-55 degrees C heating were greater in inflamed rats as compared with naive rats. A subpopulation of WDR neurons recorded from TMJ (n = 4 of 10)- or PO (n = 3 of 13)-injected rats responded to cooling in addition to heating of the RFs but did not grade their responses with changes in stimulus intensity. These results indicate that persistent orofacial inflammation produced hyperexcitability of MDH nociceptive neurons. TMJ inflammation resulted in more robust changes in MDH nociceptive neurons as compared with PO inflammation, consistent with previous studies of increased inflammation, increased MDH Fos-protein expression, and increased MDH preprodynorphin mRNA expression in this deep tissue orofacial model of pain and hyperalgesia. The inflammation-induced MDH hyperexcitability may contribute to mechanisms of persistent pain associated with orofacial deep tissue painful conditions.

Animals↗
PubMed1999

Antihyperalgesic effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan in the oral surgery model.

Peripheral neuronal barrage from tissue injury produces central nervous system hyperexcitability through the activation of N-methyl-D-aspartate (NMDA) receptor sites by excitatory amino acids and neuropeptides. This study evaluated if attenuation of NMDA receptor activation with dextromethorphan (DM) suppresses the postoperative development of hyperalgesia. Seventy-five patients undergoing oral surgery in a parallel-group, double-blind study randomly received either a placebo or the maximally tolerated dose of DM administered orally prior to and continuing for 48 hours following surgery. Pain as measured by category, visual analog, and verbal descriptor scales was not significantly different between groups during the first 6 hours following surgery. However, pain at 48 hours was decreased in the DM group as measured by scales for pain intensity and unpleasantness. Subjects in the DM group also self-administered fewer acetaminophen tablets for unrelieved pain over 24 to 48 hours postoperatively. The results suggest that DM at maximally tolerated doses does not produce an analgesic effect in the immediate postoperative period but reduces pain at 48 hours. This may be related to antagonism of NMDA receptors necessary for the expression of hyperalgesia associated with noxious afferent input postoperatively.

Adult↗
PubMed1999

Central nervous system plasticity and persistent pain.

Nerve signals arising from sites of tissue or nerve injury lead to long-term changes in the central nervous system and contribute to hyperalgesia and the amplification and persistence of pain. These nociceptor activity-induced changes are referred to as central sensitization. Central sensitization involves an increase in the excitability of medullary and spinal dorsal horn neurons brought about by a cascade of events, including neuronal depolarization, removal of the voltage-dependent magnesium block of the N-methyl-D-aspartate (NMDA) receptor, calcium entry into neurons, phosphorylation of the NMDA receptor, a change in the cell's excitability, and an increase in synaptic strength. These changes also include activation of other ionotropic and metabotropic excitatory amino acid receptors, neuropeptides such as substance P, neurotrophins, and kinases involved in the phosphorylation process. Central sensitization occurs in trigeminal nociceptive pathways, and more robust neuronal hyperexcitability occurs following deep tissue stimulation than following cutaneous stimulation. By means of Fos protein immunocytochemistry, researchers have found that 2 distinct regions are activated: the subnucleus interpolaris/caudalis transition zone (Vi/Vc) and the caudal subnucleus caudalis. The latter exhibits changes very similar to those in the spinal dorsal horn, but the Vi/Vc zone likely is involved in autonomic nervous system processing and activation of the pituitary-adrenal axis. Descending systems are also an important component of the central sensitization process and provide the neural networks by which cognitive, attentional, and motivational aspects of the pain experience modulate pain transmission. These findings of nociceptor activity-induced neuronal plasticity have important clinical implications in the development of new approaches to the management of persistent pain.

Chronic Disease↗
PubMed1998

Inflammation-induced Fos protein expression in the rat spinal cord is enhanced following dorsolateral or ventrolateral funiculus lesions.

Previous studies have shown an enhanced expression of Fos protein-like immunoreactivity in the lumbar spinal cord of rats with complete spinal transection following persistent hindpaw inflammation. To further locate the spinal pathways responsible for these effects, we compared the inflammation-evoked Fos expression in rats with bilateral lesions of the dorsolateral (DLFX) or ventrolateral (VLFX) funiculus, and with rats with a sham operation. The results indicate that the number of Fos-labeled neurons was significantly increased in all laminae of the dorsal horn ipsilateral to the inflamed hindpaw and in contralateral deep dorsal horn in both DLFX and VLFX rats compared to sham-operated rats. Moreover, when comparing DLFX and VLFX rats, in the ipsilateral spinal cord, DLFX resulted in more Fos expression in the deep dorsal horn; in contrast, a larger number of Fos-labeled cells in superficial laminae was observed in VLFX rats. These results suggest that modulatory systems, which descend in both DLF and VLF pathways, mediate the enhanced net descending nociceptive inhibition after persistent inflammation, although the supraspinal sites of origin of each pathway are likely functionally diverse.

Animals↗
PubMed1998

Ifenprodil blocks the excitatory effects of the opioid peptide dynorphin 1-17 on NMDA receptor-mediated currents in the CA3 region of the guinea pig hippocampus.

This study found that dynorphin had a biphasic concentration response relationship on N-methyl-D-aspartate (NMDA) receptor-mediated currents in the CA3 region of the guinea pig hippocampal slice. A previous study demonstrated that the inhibitory effect was mediated by a kappa 2 opioid receptor. In the present study, the polyamine site antagonist ifenprodil converted dynorphin's biphasic concentration response relationship to a monophasic inhibitory curve. The polyamine diethylenetriamine also blocked dynorphin's excitatory actions. The combination of dynorphin 1-17 and naloxone produced neurotoxicity, presumably as a result of dynorphin's excitatory actions on NMDA receptors. In addition, the release of endogenous dynorphin from mossy fibers in the presence of naloxone injured the cells. Ifenprodil prevented the neurotoxicity of both applied and released dynorphin. These findings suggest that dynorphin acts at a polyamine site to produce its excitatory effects and, further, suggest that dynorphin may mediate some neuropathologies through its interaction at this site.

Animals↗
PubMed1997

Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats.

Sweet taste and nonnutritive suckling produce analgesia to transient noxious stimuli in infant rats and humans. The present study evaluated the pain-modulating effects of sucrose and suckling in a rat model of persistent pain and hyperalgesia that mimics the response to tissue injury in humans. Fore- and hindpaw withdrawal latencies from a 30 degrees or 48 degrees C brass stylus were determined in 10-day-old rats following paw inflammation induced by complete Freund's adjuvant (CFA; 1:1 injected s.c. in a 0.01 ml volume). CFA markedly decreased escape latencies to both 48 degrees and 30 degrees C stimulation, thereby demonstrating thermal hyperalgesia and mechanical allodynia. The combination of nonnutritive suckling and sucrose (7.5%, 0.01-0.06 ml/min) infusion markedly increased escape latencies to forepaw stimulation in both CFA-treated and control rats. In contrast, intraoral sucrose and suckling did not increase hindpaw withdrawal latencies in either control or CFA-inflamed rats. The effect was specific to sweet taste because neither water nor isotonic saline infusion affected forepaw escape latencies. Parallel findings were obtained for CFA-induced Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation. Fos-LI was selectively induced in cervical and lumbar regions ipsilateral to forepaw and hindpaw inflammation, respectively. Suckling-sucrose treatment significantly reduced Fos-LI at the cervical but not at the lumbar regions. These findings demonstrate: (i) the development of persistent pain and hyperalgesia in 10-day-old rats that can be attenuated by endogenous pain-modulating systems activated by taste and nonnutritive suckling; (ii) the mediation of the sucrose-suckling analgesia and antihyperalgesia at the spinal level; and (iii) a differential rostrocaudal maturation of descending pain-modulating systems to the spinal cord of 10-day-old rats. These findings may provide new clinical approaches for engaging endogenous analgesic mechanisms in infants following tissue injury and inflammation.

Animals↗
PubMed1997

Blockade of peripheral neuronal barrage reduces postoperative pain.

Peripheral afferent neuronal barrage from tissue injury produces central nervous system hyperexcitability which may contribute to increased postoperative pain. Blockade of afferent neuronal barrage has been reported to reduce pain following some, but not all, types of surgery. This study evaluated whether blockade of sensory input with a long-acting local anesthetic reduces postoperative pain after the anesthetic effects have dissipated. Forty-eight patients underwent oral surgery with general anesthesia in a parallel group, double-blind, placebo-controlled study. Subjects randomly received either 0.5% bupivacaine or saline intraoral injections, general anesthesia was induced with propofol, a non-opioid anesthetic, and 2-4 third molars extracted. Subjects were assessed at 24 and 48 h for postoperative pain and analgesic intake. Blood samples were collected at baseline, intraoperatively and at 1-h intervals postoperatively for measurement of beta-endorphin as an index of CNS response to nociceptor input. Plasma beta-endorphin levels increased significantly from baseline to the end of surgery in the saline group in comparison to the bupivacaine group (P < 0.05), indicating effective blockade of nociceptor input into the CNS by the local anesthetic. Pain intensity was not significantly different between groups at 24 h. Pain at 48 h was decreased in the bupivacaine group as measured by category scale and graphic rating scales for pain and unpleasantness (P < 0.05). Additionally, subjects in the bupivacaine group self-administered fewer codeine tablets for unrelieved pain over 24-48 h postoperatively (P < 0.05). These data support previous animal studies demonstrating that blockade of peripheral nociceptive barrage during and immediately after tissue injury results in decreased pain at later time points. The results suggest that blockade of nociceptive input by administration of a long-acting local anesthetic decreases the development of central hyperexcitability, resulting in less pain and analgesic intake.

Adult↗
PubMed1997

Putative kappa-2 opioid agonists are antihyperalgesic in a rat model of inflammation.

It has been demonstrated that kappa-2 opioid receptor agonists can inhibit the current that flows through the N-methyl-o-aspartate (NMDA) subclass of excitatory amino acid receptor. NMDA receptor antagonists have been shown to be effective antihyperalgesic agents when administered intrathecally into rats. Antihyperalgesia is defined as the ability to block enhanced sensitivity, usually produced by nerve injury or inflammation, to nociceptive stimuli. Thus, the hypothesis was proposed that kappa-2 opioid receptor agonists would be antihyperalgesic when injected intrathecally into rats with an inflamed hind paw. The kappa agonists bremazocine and GR89,696 were effective at reversing the hyperalgesia associated with the inflamed hind paw but did not influence the sensitivity of the noninflamed hind paw to noxious heat. The kappa-1-selective agonist U69,593 had no effect on the heat sensitivity of either the inflamed paw or the noninflamed paw. Intrathecal injection of the mu-selective agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin or the delta-selective agonist [D-Pen(2,5)]enkephalin elevated paw withdrawal latencies to heat in both hind paws. These findings indicate that activation of presumed kappa-2 receptors in the rat spinal cord results in suppression of the hyperalgesic state without influencing normal sensitivity to noxious stimuli. It is proposed that the antihyperalgesic effect of kappa-2 receptor activation is mediated by the ability of the opioid receptor to reduce the flow of current through the NMDA receptor ionophore.

Analgesics↗
PubMed1996

Application of nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on injured nerve attenuates neuropathy-induced thermal hyperalgesia in rats.

This study tested the ability of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), to attenuate behavioral hyperalgesia in a rat model of neuropathic pain [Bennett, G.J. and Xie, Y.-K., Pain, 33 (1988) 87-107]. A mononeuropathy was produced by chronic constriction injury (CCI) of the sciatic nerve. Thermal hyperalgesia was assessed by a reduction of paw withdrawal latency to a noxious heat source. Following CCI, there was significant hyperalgesia in groups of rats treated with D-NAME (n = 7), an inactive isomer of L-NAME, saline (n = 7) or systemic L-NAME (n = 10). In contrast, when L-NAME was applied directly and continuously to the site of CCI (5.0 micrograms/microliter per h for up to 2 weeks) via an osmotic pump implanted at the time of the injury, no significant thermal hyperalgesia was observed (n = 8). The results suggest the involvement of nitric oxide in the development and maintenance of thermal hyperalgesia in a rat model of neuropathy. The blockade of nitric oxide production at the site of injury may provide a new approach for treatment of neuropathic pain.

Animals↗
PubMed1996

c-Jun activation of the DYNCRE3 site in the prodynorphin promoter.

The DYNCRE3 site in the prodynorphin promoter is similar to both the AP-1 and cAMP-responsive element (CRE) consensus sequences. Because c-Jun is known to bind to both AP-1 and CRE sequences, we evaluated the potential role of this transcription factor at the DYNCRE3 site using transient transfection and gel mobility shift analyses. In PC12 cells, co-transfections of a chloramphenicol acetyl transferase (CAT) reporter gene containing the DYNCRE3 site and a c-Jun expression vector resulted in transcriptional activity 9-fold greater than control. Co-transfections with a mutant c-Jun protein lacking the transactivation domain resulted in a concentration-dependent decrease in transcriptional activity. Gel mobility shift analysis demonstrated the formation of a multi-component protein-DNA complex between an oligonucleotide centered on the DYNCRE3 site and nuclear extract from untreated and forskolin-stimulated PC12 cells. The upper band of this complex could be completely supershifted with the addition of a c-Jun specific antibody. These convergent data suggest that c-Jun is involved in transcriptional activation through the DYNCRE3 site.

Animals↗
PubMed1996

An isobolographic analysis of the effects of N-methyl-D-aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat.

1. The interaction between N-methyl-D-aspartate (NMDA) and NK1 tachykinin receptors was analyzed isobolographically in rats with inflammatory hyperalgesia induced by intraplantar injection of complete Freund's adjuvant-saline emulsion (CFA, 100 micrograms Mycobacterium tuberculosis). 2. Thermal hyperalgesia of the inflamed paw, determined by paw withdrawal response to a heat stimulus, was dose-dependently attenuated by intrathecal administration of an NMDA receptor antagonist, dextrorphan (2.5-40 micrograms, ED50 = 7.2 micrograms), and two NK1 tachykinin receptor antagonists, WIN 51,708 (0.01-200 micrograms, ED50 = 10.4 micrograms) or CP-96,345 (5-200 micrograms, ED50 = 82.1 micrograms). There was no effect of these agents on the nociceptive threshold of the non-inflamed paw. CP-96,344, an enantiomer of CP-96,345 that is inactive as an NK1 tachykinin receptor antagonist, slightly attenuated hyperalgesia at a dose of 200 micrograms. 3. Combinations of dextrorphan and WIN 51,708 were administered at fixed ratios (10%:90%; 41%:59%; 90%:10%). Isobolographic analysis revealed that the ED50s obtained from the three combination ratios were not significantly different from those that were expected from a simple additive effect. 4. Thus, an additive interaction was demonstrated between NMDA and NK1 tachykinin receptor systems at the spinal level. These results suggest that both NMDA and NK1 tachykinin receptors are activated in response to peripheral inflammation, but that they may contribute independently to development of hyperalgesia.

Androstanes↗
PubMed1996

Enhanced descending modulation of nociception in rats with persistent hindpaw inflammation.

1. The role of descending brain stem modulatory systems in the development of persistent behavioral hyperalgesia and dorsal horn hyperexcitability was studied in rats with unilateral hindpaw inflammation. Inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA, 0.05 ml of an 1:1 oil/saline emulsion, 25 micrograms Mycobacterium), or lambda carrageenan (1 mg/ 0.1 ml saline). Thermal hyperalgesia was assessed by testing paw withdrawal latency (PWL) to a noxious heat stimulus. Superficial dorsal horn nociceptive (nociceptive specific, NS, and wide dynamic range, WDR) neuronal activity in the lumbar spinal cord was recorded extracellularly in chloralose-anesthetized rats. 2. Bilateral lesions of the dorsolateral funiculus (DLFX) at the T10 level were made in 13 rats, and the development of thermal hyperalgesia in these rats was compared with sham-operated or nonoperated control rats. In rats receiving a 0.05-ml CFA injection, a similar magnitude of hyperalgesia developed in the inflamed paw in DLFX (n = 7) and control (n = 8) rats. In addition, there appeared to be a contralateral hyperalgesia that was most apparent between 2 and 24 h after injection of CFA in DLFX rats. The CFA-induced contralateral effects were significantly different (P < 0.05) from the control rats at 2 and 6 h. 3. The intensity of the thermal stimulus was reduced and a low dose of carrageenan (1 mg) was injected into one hindpaw to further reveal the potentiation of hyperalgesia in DLFX rats. Throughout the 0.5- to 4-h time period after the injection of carrageenan, the PWL of the inflamed paws in DLFX rats (n = 6) was significantly shorter than that of control rats (n = 10; 2-way analysis of variance, F1,14 = 14.04, P < 0.01), suggesting the enhancement of hyperalgesia in DLFX rats. A hyperalgesia on the noninflamed paws was also more apparent in this experiment in DLFX rats, when compared with control rats. DLFX did not affect the baseline PWL of the rats. 4. A reversible spinalization was produced by application of a local anesthetic, lidocaine (2%, 0.1 ml), onto the dorsal surface of the thoracic cord (T10-12). This procedure produced thoracic spinal block that lasted for 90 min. The effects of thoracic lidocaine block on nociceptive neuronal activity were studied in 11 neurons (NS = 7, WDR = 4) in CFA-inflamed rats and 10 neurons (NS = 6, WDR = 4) in noninflamed naive rats. After the thoracic lidocaine block, rats showed increases in background activity, expansion of the receptive fields, and increased responses to noxious thermal, mechanical, and electrical stimuli. 5. Quantitative comparison revealed that the mean change in background firing rate of dorsal horn neurons was greater in inflamed [NS: 18.3 +/- 0.4 Hz, (mean +/- SE) n = 7; WDR: 10.9 +/- 0.7 Hz, n = 4] than that in noninflamed (NS: 2.3 +/- 0.3 Hz, n = 6; WDR: 3.3 +/- 0.4 Hz, n = 4) rats (P < 0.01, t-test) after thoracic lidocaine block. Thoracic saline application produced a 2.8 +/- 0.4 Hz decrease in background activity (2 NS and 2 WDR units). The expansion of the receptive fields after thoracic lidocaine block was also greater in inflamed (NS: 141 +/- 9% control, n = 6; WDR: 240 +/- 36% control, n = 4) than in noninflamed (NS: 114 +/- 9% control, n = 6; WDR: 167 +/- 21% control, n = 4) rats (P < 0.05, t-test). Thoracic saline did not produce a significant change in the receptive field size (105 +/- 9%, n = 4). The increases in responses to noxious thermal and mechanical stimuli after thoracic lidocaine block were also significantly greater in inflamed than in noninflamed rats (P < 0.01). There was no significant difference in the increase in responses to electrical stimulation of the sciatic nerve after lidocaine between inflamed and noninflamed rats.(ASTRACT TRUNCATED)

Animals↗
PubMed1996

Identifying a neurobiologic basis for drug therapy in TMDs.

Emerging results from clinical and basic research indicate that persistent pain results in changes in the central nervous system. These changes may help explain chronic orofacial pain and lead to new therapies. The authors review data that support the use of tricyclic antidepressants for neurogenic or atypical pain, and benzodiazepines for musculoskeletal pain. Dentists must weigh the benefits of the chronic administration of a drug for the management of temporomandibular disorders against the equivocal scientific support for the use of many drug classes and the potential for serious toxicity with prolonged administration.

Adrenal Cortex Hormones↗
PubMed1995

Nerve growth factor alleviates a painful peripheral neuropathy in rats.

Nerve growth factor (NGF) reverses some effects of axotomy and prevents toxic neuropathy in adult rodents. We tested the effect of NGF on behavioral hyperalgesia resulting from a chronic constriction injury (CCI) of the sciatic nerve in the rat [5]. CCI rats exhibit thermal hyperalgesia as demonstrated by a reduction of paw withdrawal latency to a noxious thermal stimulus applied to the paw on the side of injury. The mechanical sensitivity of the ipsilateral hindpaw, assessed with von Frey filaments, was also significantly increased. There were no significant changes in nociceptive thresholds on the contralateral side. When NGF was infused directly on the ligated nerve via an osmotic pump (0.5 microgram/microliter/h for 7 days) immediately after the ligation, thermal hyperalgesia was abolished from postoperative days 5 up to at least two weeks. The CCI-induced decrease in mechanical threshold was also abolished by NGF. However, NGF had only a minor effect on the abnormally long response duration, a second measure of mechanical sensitivity, to the mechanical stimulus. Delayed infusion of NGF four days after the ligation failed to block hyperalgesia. Infusion of NGF on the sciatic nerve of rats that had no CCI had no significant effect on paw withdrawal latency. Infusion of anti-NGF antiserum did not enhance hyperalgesia in CCI rats. These results suggest that alterations in neurotrophic factor(s) contribute to the development of behavioral hyperalgesia in an animal model of neuropathy and that NGF may have therapeutic value in the treatment of neuropathic pain in humans.

Animals↗
PubMed1995

UREB1, a tyrosine phosphorylated nuclear protein, inhibits p53 transactivation.

Tumor suppressor p53 is a transcription activator that upregulates target genes containing the p53 binding site. UREB1, a DNA binding protein that is tyrosine phosphorylated in vivo, shares a significant homology with the human papilloma virus E6 associated protein (E6-AP). E6-AP forms a ternary complex with E6 and p53 and participates in the ubiquitination of p53. Based on the homology with E6-AP, but taking into account the nuclear localization of UREB1 and its smaller size, the present study used a transient transfection system to examine whether UREB1 influenced p53-stimulated transcription. Co-transfection of a vector expressing wildtype UREB1 with one expressing p53 into H1299, a p53 negative cell line, resulted in a pronounced suppression of p53 transactivation. The inhibitory effect was significantly attenuated by mutation of a tyrosine residue in the consensus tyrosine phosphorylation sequence of UREB1. These data suggest that optimal suppression of p53 transactivation requires tyrosine phosphorylated UREB1 and that tyrosine phosphorylation and dephosphorylation processes may be involved in the regulation of p53 transactivation.

Amino Acid Sequence↗
PubMed1994

Neonatal capsaicin treatment in rats results in scratching behavior with skin damage: potential model of non-painful dysesthesia.

We administered capsaicin or vehicle in 2-day-old rat pups, and for over 6 months examined the rats for damaged skin and for the behaviors of scratching, gnawing and biting their skin. By 35 days of age, all rats in the capsaicin group (n = 10) had damaged skin (i.e., lesions, hair loss and red skin) on the rostral half of their bodies. Skin damage remained prevalent over 6 months, whereas vehicle-treated rats (n = 8) had virtually no skin damage. Gnawing and biting behaviors were rarely observed, however, rats in the capsaicin group frequently scratched themselves. There was a significant positive correlation between the frequency at which rats scratched themselves and the total area of skin damage. Morphine (3.0 mg/kg, i.p.) greatly increased scratching behavior in only the capsaicin-treated rats and naloxone (0.5 mg/kg, i.p.) significantly reduced scratching in these rats. Thus, neonatal capsaicin, in its destruction of the majority of primary afferent C-fibers, is capable of inducing opioid-sensitive scratching behavior.

Animals↗