The Fibromyalgia Pain Experience: A Scoping Review of the Preclinical Evidence for Replication and Treatment of the Affective and Cognitive Pain Dimensions.

Fibromyalgia is a chronic, widespread pain disorder that is strongly represented across the affective and cognitive dimensions of pain, given that the underlying pathophysiology of the disorder is yet to be identified. These affective and cognitive deficits are crucial to understanding and treating the fibromyalgia pain experience as a whole but replicating this multidimensionality on a preclinical level is challenging. To understand the underlying mechanisms, animal models are used.

The role of the male rat infralimbic cortex in distraction analgesia.

Cognitive interventions, including distraction, have been successfully utilized in the manipulation of experimental pain and the treatment of clinical pain. Attentional diversions can reduce the experience of pain, a phenomenon known as distraction analgesia (DA). Prior research has suggested that variations in stimulus intensity may influence the magnitude of DA.

Pregabalin and hyperbaric oxygen therapy on pain thresholds and anxio-depressive behaviors in a preclinical fibromyalgia pain model.

Fibromyalgia (FM) is a chronic, widespread pain disorder generally of a non-inflammatory nature with many known affective and cognitive comorbidities. There is promise in the implementation of hyperbaric oxygen therapy (HBO) for alleviating FM pain and comorbidities, despite no work investigating the efficacy of this treatment in prominent preclinical FM models. This project aimed to investigate the affective components, specifically anhedonia and anxiety, associated with an acidic saline model of FM in rats.

The Use of an FR1 Schedule Operant Approach-Avoidance Paradigm to Measure the Aversiveness of Neuropathic and Inflammatory Pain.

Pain is a subjective, private, yet universal phenomenon that depends on a unique combination of sensory, affective, and evaluative characteristics. Although preclinical models have been used to understand much of pain physiology, the inability to communicate with animals limits affective and evaluative feedback and has constrained traditional behavioral methods to adequately represent and study the multidimensional pain experience. Therefore, this study sought to characterize the affective component of pain within a novel operant approach-avoidance paradigm (AAP) to determine which type of pain (inflammatory and neuropathic) may be more aversive.

Evaluating the impact of age and inflammatory duration on behavioral assessments of nociception.

Pain is a prevalent issue for elderly individuals. Unfortunately, it remains unclear how acute and chronic pain differs as a function of age, and surprisingly, there is even disagreement on how the sensory and affective dimensions of pain change with age. Therefore, the current investigation evaluated such age differences with behavioral methodology using a preclinical model of arthritis.

A model of pain behaviors in freely moving rats generated by controllable electrical stimulation of the peripheral nerve.

Background: Neuropathic pain patients have described experiencing unprovoked, intermittent pain attacks with shooting, stabbing, and burning qualities. Rodent models used in previous literature usually only involve acute exposure, and/or are unable to manipulate the stimulation intensity in vivo by the experimenter during an experiment.

New Method: This paper describes a method to induce controllable pain behaviors in rodents using a wireless portable electronic device that can be manipulated within the course of an experiment.

Assessing the aversive nature of pain with an operant approach/avoidance paradigm.

Preclinical pain assessments can be criticized for failing to adequately characterize the human clinical pain experience. Although recent assessments have improved upon this shortcoming, there are still significant limitations. One concern is that current procedures fail to examine underlying motivational drives related to pain.

Minocycline inhibits neurogenic inflammation by blocking the effects of tumor necrosis factor-α.

It has been well established that neurogenic inflammation is one of the major pathological processes underlying inflammatory pain, but there are few effective anti-inflammatory drugs to alleviate such pain. The present study shows that minocycline, a widely used glial activation inhibitor, is effective in reducing neurogenic inflammation. Patch-clamp recordings showed that small sized dorsal root ganglion (DRG) neurons were dramatically excited following intradermal capsaicin injection in the rat hind paw, evidenced by decreased rheobase and membrane threshold.

Disruption of neurogenesis and cortical development in transgenic mice misexpressing Olig2, a gene in the Down syndrome critical region.

The basic helix-loop-helix (bHLH) transcription factor Olig2 is crucial for mammalian central nervous system development. Human ortholog OLIG2 is located in the Down syndrome critical region in trisomy 21. To investigate the effect of Olig2 misexpression on brain development, we generated a developmentally regulated Olig2-overexpressing transgenic line with a Cre/loxP system.

Pain inhibition by optogenetic activation of specific anterior cingulate cortical neurons.

Cumulative evidence from both humans and animals suggests that the anterior cingulate cortex (ACC) is important for pain-related perception, and thus a likely target for pain relief therapy. However, use of existing electrode based ACC stimulation has not significantly reduced pain, at least in part due to the lack of specificity and likely co-activation of both excitatory and inhibitory neurons. Herein, we report a dramatic reduction of pain behavior in transgenic mice by optogenetic stimulation of the inhibitory neural circuitry of the ACC expressing channelrhodopsin-2.

Behavioral neuroscience of psychological pain.

Pain is a common word used to refer to a wide range of physical and mental states sharing hedonic aversive value. Three types of pain are distinguished in this article: Physical pain, an aversive state related to actual or potential injury and disease; social pain, an aversive emotion associated to social exclusion; and psychological pain, a negative emotion induced by incentive loss. This review centers on psychological pain as studied in nonhuman animals.

The elusive rat model of conditioned placebo analgesia.

Recent research on human placebo analgesia has suggested the need for rodent models to further elucidate the neural substrates of the placebo effect. This series of 3 experiments therefore was performed in an attempt to develop a model of placebo analgesia in rats. In each study, female Sprague-Dawley rats received an L5 spinal nerve ligation to induce a neuropathic pain condition.

The anterior cingulate cortex and pain processing.

The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus.

An overview of animal models of pain: disease models and outcome measures.

Unlabelled: Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined.

Role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations.

The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cortex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following continuous vs. partial reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity.

The place escape/avoidance paradigm: a novel method to assess nociceptive processing.

This paper summarizes a behavioral paradigm that was developed as a novel method to dissociate the multidimensional pain experience in rodents. The place escape/avoidance paradigm (PEAP) is based on the assumption that if animals escape and/or avoid a noxious stimulus, then the stimulus is aversive to the animal. Data is presented showing that when animals are placed in a specific environmental condition, they will perform purposeful behavior to escape and/or avoid the noxious stimulus.

Pain affect in the absence of pain sensation: evidence of asomaesthesia after somatosensory cortex lesions in the rat.

Multidimensional models of pain processing distinguish the sensory, motivational, and affective components of the pain experience. Efforts to understand underlying mechanisms have focused on isolating the roles of specific brain structures, including both limbic and non-limbic cortical areas, in the processing of nociceptive stimuli. The purpose of this study was to examine the role of the somatosensory cortex in both sensory and affective aspects of pain processing.

Evaluating underlying neuronal activity associated with escape/avoidance behavior in response to noxious stimulation in adult rats.

The place escape/avoidance paradigm (PEAP) is a behavioral test designed to quantify the level of unpleasantness evoked by painful stimuli by assessing the willingness of a subject to escape/avoid a preferred area when it is associated with noxious stimulation. Previous studies have demonstrated that escape/avoidance behavior is dependent on activity in the anterior cingulate cortex (ACC), a region of the limbic system involved in processing the emotional component of pain in humans and animals. Analysis of c-Fos expression in the ACC confirmed that the escape/avoidance response to noxious stimuli corresponds to changes in neural activation in this region.

Impairment of recovery from incentive downshift after lesions of the anterior cingulate cortex: emotional or cognitive deficits?

The anterior cinculate cortex (ACC) is known to be implicated in pain-fear and reward expectations. Animals were given electrolytic lesions of the ACC and then trained in the consummatory successive negative contrast (cSNC) situation. In cSNC, animals exposed to an incentive downshift from 32% to 4% sucrose exhibit less consummatory behavior than animals always exposed to 4% sucrose.

Chronic administration of phencyclidine produces decreased sensitivity to mechanical stimulation in the absence of altered affective behavior: Implications for pain processing in schizophrenia.

Patients with schizophrenia have been shown to display decreased sensitivity to pain, which can severely compound the impact of injuries and illnesses. Alterations in the sensory and affective systems of pain processing have been proposed as mechanisms, but the unique contribution of each of these systems has not been elucidated. The aim of this study was to investigate these two components of pain using the NMDA receptor antagonist, phencyclidine (PCP), an established animal model of schizophrenia.

Chronic inflammatory pain does not attenuate the development of tolerance to chronic morphine in adult male rats.

The overall impact of chronic pain on the response to opioids is ambiguous in the literature, and comparisons between human and animal studies are complicated by vast differences between the manner and dosage of opioids given to humans treated for pain in comparison to rodents as well as a lack of healthy participant studies examining the impact of chronic opioids. The purpose of this study was to evaluate the impact of chronic pain on the development of tolerance to morphine and to assess how the concentration of drug affects this process. Twenty-four hours after the injection of CFA or normal saline in the left hind paw, the level of mechanical hypersensitivity was assessed and animals were randomly assigned to a morphine dose (1, 3 or 8 mg/kg or saline).

Maternal separation stress leads to enhanced emotional responses to noxious stimuli in adult rats.

The purpose of the current study was to examine pain processing in adult rats following repeated maternal separation in infancy, a common model of early life stress. Sensory pain processing remained unaltered, as measured using threshold testing of nociception. However, affective pain processing was enhanced as revealed by increased responding during the tonic phase of the formalin test and during the place escape/avoidance test.

Hyperbaric oxygen treatment decreases pain in two nerve injury models.

Hyperbaric oxygen (HBO) treatment has been used clinically to treat a variety of ailments, including severe burns and carbon monoxide poisoning, and in research settings has produced promising results when used to treat animal models of inflammatory pain. However, studies examining neuropathic pain or nerve injury models have been limited to physiological assessments and not whether the pain condition improves. The purpose of this study was to evaluate the effect of HBO on two common models of neuropathic pain, L5 ligation and chronic constriction injury (CCI) of the sciatic nerve.

Naltrexone fails to increase pain affect in response to inflammatory pain in a novel escape/avoidance paradigm.

The non-specific opioid antagonist naltrexone has traditionally been used as treatment for opioid overdose, as well as in research settings as an antagonist to examine opioid and non-opioid mediated analgesia. However, the mechanisms by which this drug operates are not well understood, and its exact effects on sensory and affective pain processes remain uncertain. Various studies have demonstrated that naltrexone behaves in a paradoxical manner, leading to analgesia, no discernable changes, or an increase in pain, depending on the circumstances of the study.

Differential effects of paclitaxel treatment on cognitive functioning and mechanical sensitivity.

Treatment for cancer has been indicated to negatively impact the quality of life for patients. Specifically, chemotherapy has been associated with fatigue, nausea, and peripheral neuropathy. More recently, chemotherapy has been found to be related to cognitive impairment in various domains including working memory, information processing speed, and visual attention.