Depressive-like States Heighten the Aversion to Painful Stimuli in a Rat Model of Comorbid Chronic Pain and Depression

Bravo, Lidia; Micó, Juan Antonio; Rey-Brea, Raquel; Perez‐Nievas, Beatriz Gomez; Leza, Juan C.; Berrocoso, Esther

doi:10.1097/aln.0b013e3182657b3e

Cited by 88 publications

(60 citation statements)

References 61 publications

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“…We first performed a behavioral analyses of each experimental groups and in agreement with our previous findings (Bravo et al, 2012) no differences in mechanical or cold allodynia in the injured hind-paw were observed between the two groups subjected to neuropathic pain (CCI-control and CCI-CMS; Figure 1D and F). In both CMS groups (sham-CMS and CCI-CMS), we detected cold but not mechanical allodynia in the non-injured paw ( Figure 1G and E).…”

Section: Resultssupporting

confidence: 78%

“…However, although no differences were detected between groups, it is likely that depressive-like behavior developed earlier in the co-morbid situation. We previously demonstrated increased avoidance of painful paw stimulation in animals exhibiting depressive-like behavior (Bravo et al, 2012), suggesting that LC impairment might contribute to the augmented perception of pain in CCI-CMS vs. CCI-control.…”

Section: Discussionmentioning

confidence: 99%

“…Cold allodynia was measured using the acetone test, whereby a 100 ml drop of acetone was applied to the center of the hindpaw with a pipette, and the response was graded to a four-point scale: 0, no response; 1, paw withdrawal; 2, repeated paw flicking; 3, paw licking. The mean score value was calculated according to: (summation score value of each trials/ number of total trials) (Bravo et al, 2012).…”

Section: Behavioral Testsmentioning

confidence: 99%

“…Rats were placed for 15 min in Plexiglas cylinders filled with 30 cm of water (pre-test session), and again for 5 min 24 h later (test session). The animal 0 s behavior (immobility, swimming or climbing) was assessed throughout the test session (Bravo et al, 2012;Detke et al, 1995). Administration of the noradrenaline reuptake inhibitor, desipramine (20 mg/kg, i.p.…”

Section: Behavioral Testsmentioning

confidence: 99%

“…It is unclear whether depression and chronic pain are causally related, or whether diagnosis with one condition implies a predisposition to the other. We previously investigated the complex relationship between these conditions in animal models of depression, pain, and co-morbid depression and pain (Bravo et al, 2012). In rats subjected to chronic mild stress (CMS), which induces depressive-like behavior, we observed minimal changes in sensorial pain perception.…”

Section: Introductionmentioning

confidence: 99%

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Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Bravo

Torres-Sánchez

Alba-Delgado

et al. 2014

European Neuropsychopharmacology

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Depression can influence pain and vice versa, yet the biological mechanisms underlying how one influences the pathophysiology of the other remains unclear. Dysregulation of locus coeruleusnoradrenergic transmission is implicated in both conditions, although it is not known whether this effect is exacerbated in cases of co-morbid depression and chronic pain. We studied locus coeruleus activity using immunofluorescence and electrophysiological approaches in rats subjected to unpredictable chronic mild stress (CMS, an experimental model of depression) and/or chronic constriction injury (CCI, a model of chronic neuropathic pain) for 2 weeks. CCI alone had no effect on any of the locus coeruleus parameters studied, while CMS led to a slight reduction in the electrophysiological activity of the locus coeruleus. Furthermore, CMS was associated with an increase in the number of tyrosine hydroxylase-positive cells in the locus coeruleus, although they were smaller in size. Interestingly, these effects of CMS were exacerbated when combined with CCI, even though no changes in the α2-adrenoreceptors or the noradrenaline transporter were observed in any group. Together, these findings suggest that CMS triggers several modifications in locus coeruleus-noradrenergic transmission that are exacerbated by co-morbid chronic pain. & 2014 Elsevier B.V. and ECNP. All rights reserved. E-mail address: esther.berrocoso@uca.es (E. Berrocoso). European Neuropsychopharmacology (]]]]) ], ]]]-]]]Please cite this article as: Bravo, L., et al., Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats. European Neuropsychopharmacology (2014), http://dx

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Section: Resultssupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Behavioral Testsmentioning

confidence: 99%

Section: Behavioral Testsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Bravo

Torres-Sánchez

Alba-Delgado

et al. 2014

European Neuropsychopharmacology

Self Cite

View full text Add to dashboard Cite

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Psychiatric comorbidities among individuals with HIV and chronic pain

Roy¹,

Clark²,

Treisman³

2016

Chronic Pain and HIV

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Effects of S 38093, an antagonist/inverse agonist of histamine H3 receptors, in models of neuropathic pain in rats

Chaumette

Chapuy

Berrocoso

et al. 2017

European Journal of Pain

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Background: Histamine H3 receptors are mainly expressed on CNS neurons, particularly along the nociceptive pathways. The potential involvement of these receptors in pain processing has been suggested using H3 receptor inverse agonists. Methods: The antinociceptive effect of S 38093, a novel inverse agonist of H3 receptors, has been evaluated in several neuropathic pain models in rat and compared with those of gabapentin and pregabalin. Results: While S 38093 did not change vocalization thresholds to paw pressure in healthy rats, it exhibited a significant antihyperalgesic effect in the Streptozocin-induced diabetic (STZ) neuropathy model after acute and chronic administration and, in the chronic constriction injury (CCI) model only after chronic administration, submitted to the paw-pressure test. Acute S 38093 administration at all doses tested displayed a significant cold antiallodynic effect in a model of acute or repeated administration of oxaliplatin-induced neuropathy submitted to cold tail immersion, cold allodynia being the main side effect of oxaliplatin in patients. The effect of S 38093 increased following chronic administration (i.e. twice a day during 5 days) in the CCI and STZ models except in the oxaliplatin models where its effect was already maximal from the first administration The kinetics and size of effect of S 38093 were similar to gabapentin and/or pregabalin. Finally, the antinociceptive effect of S 38093 could be partially mediated by a2 adrenoreceptors desensitization in the locus coeruleus. Conclusions: These results highlight the interest of S 38093 to relieve neuropathic pain and warrant clinical trials especially in chemotherapeutic agent-induced neuropathic pain. Significance: S 38093, a new H3 antagonist/inverse agonist, displays antiallodynic and antihyperalgesic effect in neuropathic pain, especially in oxaliplatin-induced neuropathy after chronic administration. This effect of S 38093 in neuropathic pain could be partly mediated by a2 receptors desensitization in the locus coeruleus.

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Depressive-like States Heighten the Aversion to Painful Stimuli in a Rat Model of Comorbid Chronic Pain and Depression

Abstract: These findings support the theory that depression leads to emotional dysfunction in the interpretation of pain in patients suffering chronic pain. In addition, combined animal models of pain-depression may provide a valuable tool to study the comorbidity of pain and depression.

Cited by 88 publications

References 61 publications

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Pain exacerbates chronic mild stress-induced changes in noradrenergic transmission in rats

Psychiatric comorbidities among individuals with HIV and chronic pain

Effects of S 38093, an antagonist/inverse agonist of histamine H3 receptors, in models of neuropathic pain in rats

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