The role of the noradrenergic system in the affective sphere of chronic neuropathic pain

Resumen

Chronic pain is a complex experience comprising two different components: sensorial and affective components of pain. Chronic pain can become maladaptive and incapacitating leading to a worsening in the prognosis, the response to treatment and reducing life quality of patients. Furthermore, many psychobiological factors get worse the affective component of pain leading to depressive symptoms. However, little is known about the possible modifications of pain processing when chronic pain condition manifests symptoms of depression. Noradrenergic system is a pivotal candidate projecting descending and ascending regulating sensorial and emotional aspects of pain, respectively. In the present study, we assessed the role of noradrenergic system in the sensorial and emotional components of pain in rats submitted to chronic pain and/or depression. Chronic constriction injury (CCI) [1] was used as a model of chronic neuropathic pain and chronic mild stress (CMS) as a model of depression, generating four experimental groups: Sham-control, Sham-CMS, CCI-control and CCI-CMS. Parallel, in order to study the involvement of noradrenergic system in the sensorial and affective components of pain, DSP-4 (50 mg/kg), a neurotoxin which selectively damages noradrenergic projections and desipramine (DMI, 10 mg/kg), a noradrenaline reuptake inhibitor, were administered intraperitoneally to CCI-control and CCI-CMS groups the same day of CCI and CMS induction. After 14 days of treatment, sensorial and affective componentsof pain were evaluated by using nociceptive tests (von Frey and acetone test) as well as the place escape avoidance test(PEAT) [3], respectively. Additionally, we evaluated anhedonia in all experimental groups. All results were analyzed using two-way analysis of variance (ANOVA) with or without repeated measures, as appropriate. The results revealed that the group with chronic pain and depression (CCI-CMS) showed the most negative pain experience in the PEAT followed by the group with chronic pain (CCI-control). However, DMI administration prevented the worsening of affective component of pain experimented by CCIcontrol and CCI-CMS groups. Interestingly, DSP-4 administration enhancement the negative pain experience in CCI-control group showing similar score that CCI-CMS in the PEAT. Regarding to the sensory component of pain, both CCI-control and CCICMS groups showing similar degree of mechanical allodynia in the von Frey test. DMI administration prevented the development of allodynia while DSP-4 did not show significant changes in nociceptive threshold. On the other hand, both Sham-CMS and CCI-CMS development anhedonia after 14 days of CMS and DMI prevented it. Interestingly, DSP-4 administration induced anhedonia in CCI-control and enhancement anhedonia in CCICMS group. In conclusion, depression highly determines affective-pain experience and the inhibition of noradrenaline reuptake prevents it. On the other hand, the destruction of noradrenergic system, by DSP-4 administration, enhancement the negative pain experience leading to a concomitant state of chronic pain and depression. Overall suggests that noradrenergic system play a major role regulating the affective-interpretative pain experience.