Classical conditioning and pain: Conditioned analgesia and hyperalgesia

Míguez, Gonzalo; Laborda, Mario A.; Miller, Ralph R.

doi:10.1016/j.actpsy.2013.10.009

Cited by 39 publications

(28 citation statements)

References 155 publications

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“…A reduced pain perception is a classic effect produced by a variety of acute stressors in humans and animal models (Miguez et al 2014). However, stress is reported to inhibit or exacerbate pain perception depending on the nature and/or parameters of the stressor (Butler and Finn 2009).…”

Section: Discussionmentioning

confidence: 99%

Effects of social stress and clomipramine on emotional memory in mice

Duque¹,

Vinader‐Caerols²,

Monleón³

2016

Acta Neurobiologiae Experimentalis

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We have previously observed impairing effects of social defeat stress (CSDS) on inhibitory avoidance (IA) in mice. Given the similarity between changes produced by social stress in animals and symptoms of certain human psychopathologies such as depression and anxiety, the effects of the antidepressant clomipramine on IA impairment produced by CSDS were evaluated in the present study.Male CD1 mice were randomly assigned to the groups: non-stressed+saline, non-stressed+clomipramine, stressed+saline and stressed+clomipramine. Stressed animals were subjected to daily agonistic encounters (10 min) in the home cage of the aggressor over a 20-day period. Just before each encounter, non-stressed and stressed mice were injected i.p. with saline or clomipramine (10 mg/kg) according to their experimental condition. 24 hours after the last CSDS session, all the mice were tested in a step-through IA task. In the IA training phase, animals were punished by a shock to the paw when they entered the dark compartment of the apparatus. In the IA test phase (one week later) the same procedure took place, but without shock. Complementary measures were obtained by evaluating all the animals in an elevated plus maze (locomotor activity and emotionality) and on a hot plate (analgesia). IA learning was confirmed in all groups except the stressed+saline group, which was the only one that exhibited higher anxiety levels. No variations were observed in either locomotor activity or analgesia. In conclusion, CSDS induces anxiety and impairs emotional memory in mice; the negative effects of CSDS on memory appear to be attenuated by clomipramine, and these detrimental effects do not seem to be secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

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Section: Discussionmentioning

confidence: 99%

Effects of social stress and clomipramine on emotional memory in mice

Duque¹,

Vinader‐Caerols²,

Monleón³

2016

Acta Neurobiologiae Experimentalis

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“…Furthermore, both studies used a simultaneous conditioning paradigm in which CS and US were presented at the same time. This approach excludes expectation or changes in arousal -to which shifts in pain thresholds have been attributed in other classical conditioning studies (Harvie et al 2016a;Miguez et al 2014) -as the mechanism of effect. Indeed, the simultaneous approach seems well suited to model chronic pain as the real-world CS (e.g.…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Modulating pain thresholds through classical conditioning (v0.1)"

Timmers¹

2019

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Background. Classical conditioning has frequently been shown to be capable of evoking fear of pain and avoidance behaviour in the context of chronic pain. However, whether pain itself can be conditioned has rarely been investigated and remains a matter of debate. Therefore, the present study investigated whether pain threshold ratings can be modified by the presence of conditioned non-nociceptive sensory stimuli in healthy participant. Methods. In 51 healthy volunteers, pain threshold to electrocutaneous stimuli was determined prior to participation in a simultaneous conditioning paradigm. Participants underwent an acquisition phase in which one non-painful vibrotactile stimulus (CS +) was repeatedly paired with a painful electrocutaneous stimulus, whereas a second vibrotactile stimulus of the same quality and intensity (CS-) was paired with a non-painful electrocutaneous stimulus. Stimulation was provided on the lower back with close proximity between the CSs and the US. In the test phase, electrocutaneous stimuli at the individually-set threshold intensity were simultaneously delivered together with either a CS + or CS-. Pain intensity ratings were obtained after each trial; expectancy ratings were obtained after each block. The primary outcome was the percentage of test stimuli that were rated as painful. Results. Test stimuli were more likely to be rated as painful when they were paired with the CS + than when they were paired with the CS-. This effect was not influenced by contingency awareness, nor by expectancies or mood states. Discussion. The findings support the notion that the judgement of an event being painful or non-painful can be influenced by classical conditioning and corroborate the possible role of associative learning in the development and maintenance of chronic pain.

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“…Acute stress and acute stress-associated corticosterone release in rats has, by and large, been shown to inhibit nociception, while chronic stress has been linked to hyperalgesia (Imbe et al, 2006), although analgesic effects have also been repeatedly reported (reviewed in (Miguez et al, 2014). Clinically, chronic stress has also been associated with chronic pain conditions such as fibromyalgia, chronic headache, inflammatory bowel disease and tempromandibular joint pain (McEwen and Kalia, 2010).…”

Section: Introductionmentioning

confidence: 99%

Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain

Lewis¹,

Hutchinson²,

Frick³

et al. 2015

Brain, Behavior, and Immunity

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We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signalling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and tempromandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest.

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Classical conditioning and pain: Conditioned analgesia and hyperalgesia

Cited by 39 publications

References 155 publications

Effects of social stress and clomipramine on emotional memory in mice

Effects of social stress and clomipramine on emotional memory in mice

Peer Review #1 of "Modulating pain thresholds through classical conditioning (v0.1)"

Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain

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