The Occurrence of Pain-Induced Depression Is Different between Rat Models of Inflammatory and Neuropathic Pain.

Yung-Chi Hsu,Bo-Feng Lin,Kuo-Hsing Ma,Chien-Sung Tsai,Shu-Lin Guo,Chun-Chang Yeh

doi:10.3390/jcm10174016

Abstract

Various pain conditions may be associated with depressed mood. However, the effect of inflammatory or neuropathic pain on depression-like behavior and its associated time frame has not been well established in rat models. This frontward study investigated the differences in pain behavior, depression-like behavior, and serotonin transporter (SERT) distribution in the brain between rats subjected to spared nerve injury (SNI)-induced neuropathic pain or complete Freund’s adjuvant (CFA)-induced inflammatory pain. A dynamic plantar aesthesiometer and an acetone spray test were used to evaluate mechanical and cold allodynia responses, and depression-like behavior was examined using a forced swimming test and sucrose preference test. We also investigated SERT expression by using positron emission tomography. We found that the inflammation-induced pain was less severe than neuropathic pain from days 3 to 28 after induced pain; however, the CFA-injected rats exhibited more noticeable depression-like behavior and had significantly reduced SERT expression in the brain regions (thalamus and striatum) at an early stage (on days 14, 21, and 28 in two groups of CFA-injected rats versus day 28 in SNI rats). We speculated that not only the pain response after initial injury but also the subsequent neuroinflammation may have been the crucial factors influencing depression-like behavior in rats.

Highlights

Pain is one of the main reasons that patients seek medical treatment, and it is a major clinical, social, and economic problem
This study revealed that rats subjected to neuropathic pain after spared nerve injury (SNI) or inflammatory pain after complete Freund’s adjuvant (CFA) injection exhibited pain behavior
We further found that decreased SUR of the serotonin transporter (SERT) expression in the thalamus and striatum was consistent with the appearance of depression-like behavior in the CFA-induced pain model, which manifested earlier than in the SNI-induced pain model, implying that inflammation rather than pain is responsible for the depressive behavior

Summary

Introduction

Pain is one of the main reasons that patients seek medical treatment, and it is a major clinical, social, and economic problem. Chronic pain can cause sleep disturbance, anxiety, and depression [1]. Neuropathic pain can take the form of hyperalgesia, allodynia, or persistent spontaneous pain after a nerve injury [3]. Inflammatory pain is a natural physiological response to tissue injury or infection. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings and can lead to the development of allodynia, hyperalgesia, or depression [4]. Clinical neuropathic pain is usually accompanied by anxiety and depression [5]. Anti-inflammatory medication is the main treatment option for inflammatory pain, but such medication often offers little relief from such pain and can cause side effects

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