Social defeat stress potentiates thermal sensitivity in operant models of pain processing

Abstract

Higher-order processing of nociceptive input is distributed in corticolimbic regions of the brain, including the anterior cingulate, parieto-insular and prefrontal cortices, as well as subcortical structures such as the bed nucleus of stria terminalis and amygdala. In addition to their role in pain processing, these regions encode or modulate emotional, motivational and sensory responses to stress. Thus, pain and stress pathways in the brain intersect at cortical and subcortical forebrain structures. Accordingly, previous work has shown that acute restraint stress in female rats induces heat hyperalgesia in a forebrain-dependent operant test of thermal escape. In the present study, we investigated the effects of social defeat stress in male rats on the operant escape task, as well as in a test of nociceptive thermal preference. After establishing baseline behaviors in these tests, separate groups of rats were socially defeated by dominant “resident” male rats. They were tested for thermal preference after 5 successive social defeat sessions. Escape from cold, heat and a neutral warm temperature also was evaluated after social defeat. Defeated rats exhibited a significant increase in cold preference after social defeat compared to the baseline. In the escape task, the rats exhibited increased escape from warm and nociceptive cold and heat temperatures. Thus, chronic social stress produces hyperalgesia for both hot and cold stimuli in male rats, suggesting a mutually facilitatory cross-regulation between central pathways regulating stress and pain.

CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the hindpaw

“…Stress is known to alter pain perception (Winston et al, 2009;Nasu et al, 2009;Vierck et al, 2009;Marcinkiewcz et al, 2009), and although previous studies (King et al, 2005) have demonstrated the reduction of cortisol levels in the rat with training, it is possible that an inhibitory process reduces cortisol levels while stress is still present. Bardin et al (2009) studied the effects of chronic restraint on a rat model of chronic pain.…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…Preclinical studies of SIH are essential for our understanding of the mechanisms underpinning stress-related pain syndromes and for the identification of neural pathways and substrates, and the development of novel therapeutic agents for their clinical management. The models of SIH have been described in detail in the Table 1.1 below and also further information is available in (Quintero et al, 2011(Quintero et al, , 2003(Quintero et al, , 2000Suarez-Roca et al, 2008, 2006b Carrageenan intra-muscular injection followed by grip strength Tail flick test Thermal hyperalgesia in males, no effect in females (Gamaro et al, 1998) Acute: 15mins, 30mins or 1hr Formalin injection into the Increased inflammatory (Gameiro et al, 2006) Male Wistar rats (Andre et al, 2005;Marcinkiewcz et al, 2009) …”

Selective ablation of mu-opioid receptor expressing neurons in the rostral ventromedial medulla attenuates stress-induced mechanical hypersensitivity

“…repeated social defeat). After five sessions of social defeat stress, defensive-intruders displayed hyperalgesia to both cold and heat stimuli (Marcinkiewcz et al, 2009) as well as to mechanical hind paw stimulation (Rivat et al, 2010). The number of sessions required to produce hyperalgesia in animals undergoing repeated social defeat are similar to that observed with repeated WPS.…”

“…Additional findings implicated painfacilitating neurons in this stress-induced mechanical hypersensitivity, as the increase in hind paw responses were found to involve MOR expressing neurons located within the RVM. Chronic, non-noxious stressors in particular have been shown to elicit long-lasting hyperalgesia (Andre et al, 2005;Bardin et al, 2009;da Silva Torres et al, 2003;Gamaro et al, 1998;Gameiro et al, 2006;Imbe et al, 2004;Marcinkiewcz et al, 2009;Quintero et al, 2000;Satoh et al, 1992). For example, chronic restraint stress has resulted in mechanical allodynia, heat and cold thermal hyperalgesia, and increased behavioral responses to formalin (da Silva Torres et al, 2003;Gamaro et al, 1998;Quintero et al, 2000;Satoh et al, 1992).…”

“…In contrast to SIA, animal models that employ chronic-stress, including repeated exposure to a cold environment (Satoh et al, 1992), repeated restraint stress (da Silva Torres et al, 2003;Gamaro et al, 1998;Imbe et al, 2004), repeated forced swim stress (Quintero et al, 2000), and repeated social defeat (Andre et al, 2005;Marcinkiewcz et al, 2009;Rivat et al, 2010) can elicit stress-induced hyperalgesia (SIH). While it is well documented that pain inhibitory systems descending from the brainstem to the spinal cord and medullary dorsal horn underlie SIA (Millan, 2002;Watkins and Mayer, 1982), less is known regarding the neural circuitry through which chronic stress produces hyperalgesia.…”