Chronic Pain Leads to Concomitant Noradrenergic Impairment and Mood Disorders

Alba-Delgado, Cristina; Llorca-Torralba, Meritxell; Horrillo, I.; Ortega, Jorge E.; Micó, J.A.; Sánchez‐Blázquez, Pilar; Meana, J. Javier; Berrocoso, Esther

doi:10.1016/j.biopsych.2012.06.033

Cited by 155 publications

(137 citation statements)

References 62 publications

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“…This might also be the case in our model of stress, possibly because this short period of isolation alone is insufficient to trigger a stress response in adult animals or alternatively, because adaptive changes had already developed. On the other hand, while we did not find any change in TH expression 2 weeks after CCI, an increase was evident in group-housed rats after 4 weeks [2]. This suggests that isolation might advance the changes observed 4 weeks after neuropathy is induced.…”

Section: Discussioncontrasting

confidence: 78%

“…We previously found that 2 weeks of neuropathic pain and chronic mild stress selectively increased the aversion to painful stimuli, without affecting classic depressive-like behaviours measured through the forced swimming and anhedonia test [10]. Thus, these and previous data corroborate that it takes approximately 4 weeks for rats to develop affective disorders (anxiety and depression) in association with neuropathic pain [2,19,37,43]. Nevertheless, further studies will be necessary to explore the effect of stress on the pain dimensions and secondary affective disorders over longer periods.…”

Section: Discussionsupporting

confidence: 71%

“…One set of animals was tested 5 weeks after stress in the place escape/avoidance test (PEAT) to explore the affective-cognitive dimension of pain [2,23]. Animals were placed in the centre of a 60 Â 30 Â 30 cm Plexiglas chamber on an elevated metal grid.…”

Section: Emotional Behavioural Testingmentioning

confidence: 99%

“…To evaluate anxiety-like behaviour, the elevated zero maze test was performed after 5 weeks of stress [2]. After the animals were placed in a closed section, they were allowed to investigate the maze for 5 minutes, during which the time spent in the open zone was evaluated.…”

Section: Emotional Behavioural Testingmentioning

confidence: 99%

“…In addition, it is a structure that is essential to the cognitive branch of the stress response and it is thought to be dysregulated in mental disorders such as depression, anxiety, and posttraumatic stress disorder [24,40]. In this sense, we have recently shown that long-term neuropathic pain leads to anxio-depressive-like behaviour that is temporally accompanied by an impairment of the LC [2]. Moreover, antidepressants that inhibit the reuptake of noradrenaline can normalize the nociceptive-evoked responses of LC neurons in rats that experience neuropathic pain [3].…”

Section: Introductionmentioning

confidence: 99%

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Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

Bravo

Alba-Delgado

Torres-Sánchez

et al. 2013

Pain

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a b s t r a c tStressful experiences seem to negatively influence pain perception through as yet unknown mechanisms. As the noradrenergic locus coeruleus (LC) nucleus coordinates many components of the stress response, as well as nociceptive transmission, we evaluated whether the sensory and affective dimension of chronic neuropathic pain worsens in situations of stress due to adaptive changes of LC neurons. Accordingly, male rats were socially isolated for 5 weeks, and in the last 2 weeks, neuropathic pain was induced by chronic constriction injury. In this situation of stress, chronic pain selectively heightened the animal's aversion to painful experiences (affective pain), as measured in the place escape/avoidance test, although no changes were observed in the sensory dimension of pain. In addition, electrophysiological recordings of LC neurons showed a low tonic but exacerbated nociceptive-evoked activity when the injured paw was stimulated. These changes were accompanied by an increase in tyrosine hydroxylase and gephyrin expression in the LC. Furthermore, intra-LC administration of bicuculline, a c-aminobutyric acid-A receptor antagonist, attenuated the negative affective effects of pain. These data show that changes in the LC are greater than those expected from the simple summation of each independent factor (pain and stress), revealing mechanisms through which stressors may exacerbate pain perception without affecting the sensorial dimension. Ó

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionsupporting

confidence: 71%

Section: Emotional Behavioural Testingmentioning

confidence: 99%

Section: Emotional Behavioural Testingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

Bravo

Alba-Delgado

Torres-Sánchez

et al. 2013

Pain

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Irritable Bowel Syndrome

Videlock¹,

Chang²

2015

Yamada' S Textbook of Gastroenterology

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Chronic pain and long‐term dementia risk in older adults: Results from a 24‐year longitudinal study

Rouch

Edjolo

Laurent

et al. 2022

Int J Geriat Psychiatry

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Introduction: Chronic pain (CP) was associated with cognitive impairment in previous studies. However, the longitudinal association between CP and dementia remains under debate. We aimed to assess the prospective link between CP and long-term dementia risk in a population-based cohort of older participants, considering covariables linked to CP and cognitive functioning. Methods:The study sample was selected from the PAQUID study, an ongoing cohort of older community-dwellers aged 65 years and over at baseline; Information regarding CP and analgesics consumption was collected using questionnaires. Dementia was clinically assessed every 2 years. The population was divided into 4 groups according to CP and analgesic drugs intake (CP+/A+, CP+/A−, CP−/A+, CP −/A−). An illness-death model was used to estimate the link between CP and incident dementia risk controlled for sex, educational level, comorbidities, depression, antidepressant drugs and analgesics.Results: Five hundred ninety three participants (364 women) who completed a CP questionnaire, were included. They were followed-up over 24 years (mean followup: 11.3 years, SD 7.3). A total of 223 participants (32.5%) had CP, among them 88 (38.6%) took analgesic drugs. Compared to CP−/A− group, CP+/A+ participants had a higher risk of developing dementia in the univariate model (hazard ratio (HR) = 1.73, 95%CI:1.18-2.56; p = 0.0051). However, these results did not persist in the multivariate models (aHR = 1.23, 95%CI:0.88-1.73; p = 0.23). No significant risk for dementia were observed in CP−/A+ and CP+/A− (HR = 1.30, 95%CI:0.84-2.01; p = 0.23 and HR = 1.36, 95%CI:0.95-1.96; p = 0.09, respectively). Conclusion:Our results failed to show a significant relationship between the presence of CP and long-term dementia risk, suggesting that the cognitive decline associated with CP observed in the literature does not appear to be related to Alzheimer's disease or related disorders.

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Chronic Pain Leads to Concomitant Noradrenergic Impairment and Mood Disorders

Cited by 155 publications

References 62 publications

Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

Irritable Bowel Syndrome

Chronic pain and long‐term dementia risk in older adults: Results from a 24‐year longitudinal study

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