Effects of environmental enrichment on peripheral neuropathy induced in rats.

Author(s)

Louise Faggionato Kimura Vieira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2018-05-10

Examining board members

Gisele Picolo; Rosana Camarini; Erich Talamoni Fonoff; Carolina Demarchi Munhoz; Carlos Amilcar Parada

• Advisor: Gisele Picolo

Abstract

Environmental enrichment (EE) is capable of altering the perception of nociceptive stimuli, as well as increasing the analgesic response induced by opioids. Considering that neuropathic pain is a serious public health problem and the treatment for this condition is still unsatisfactory and induces severe side effects, the aims of this study were to evaluate the interference of animal welfare in the sensitivity to different nociceptive stimuli and to investigate possible mechanisms involved in this effect. Animals were submitted to the evaluation of anxiety and pain sensitivity in a model of neuropathic pain, against mechanical and thermal nociceptive stimuli. It was seen that an elaborated EE starting from birth was able to totally reverse the neuropathic pain of animals submitted to chronic constriction injury of the sciatic nerve (CCI). This effect was completely abolished when enriched animals were treated with naloxone, a nonselective opioid antagonist. Western blot analysis did not show differences in opioid receptor expression in regions related to pain processing and control, however, circulating levels of beta-endorphin and met-enkephalin were increased in the presence of chronic pain in enriched animals. Serum corticosterone levels were also increased in animals with EE regardless of neuropathy, but treatment with mifepristone, a nonselective glucocorticoid receptor antagonist, did not alter the analgesia of operated animals. Moreover, EE reduced serotonin immunoreactivity in the spinal cord of CCI animals. In addition to analgesic effect, EE also reduced the neuronal injury marker ATF-3 at the dorsal root ganglia and, at the site of constriction, decreased the neuronal degeneration characteristic of the model, inducing the presence of M2 macrophages subtype predominantly. This work reinforces the importance of well-being in preventing the development of neuropathic pain and shows a non-pharmacological approach that may increase animal resilience against noxious stimuli. (AU)

• FAPESP's process: 13/20795-8 - Influence of environmental enrichment on pain sensitivity in animals and in its control: possible interference in the expression and activation of opioid receptors
• Grantee: Louise Faggionato Kimura Vieira
• Support Opportunities: Scholarships in Brazil - Doctorate