Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.

The representation of pain in the cerebral cortex is less well understood than that of any other sensory system. However, with the use of magnetic resonance imaging and positron emission tomography in humans, it has now been demonstrated that painful heat causes significant activation of the contralateral anterior cingulate, secondary somatosensory, and primary somatosensory cortices. This contrasts with the predominant activation of primary somatosensory cortex caused by vibrotactile stimuli in similar experiments. Furthermore, the unilateral cingulate activation indicates that this forebrain area, thought to regulate emotions, contains an unexpectedly specific representation of pain.

Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions.a Antidepressant response to ketamine was defined as a $50% improvement in Montgomery-Åsberg Depression Rating Scale total score from baseline to post-phase 2 assessment.

No abstract

Practice research networks may be one way of advancing knowledge translation and exchange (KTE) in psychotherapy. In this study, we document this process by first asking clinicians what they want from psychotherapy research. Eighty-two psychotherapists in 10 focus groups identified and discussed psychotherapy research topics relevant to their practices. An analysis of these discussions led to the development of 41 survey items. In an online survey, 1,019 participants, mostly practicing clinicians, rated the importance to their clinical work of these 41 psychotherapy research topics. Ratings were reduced using a principal components analysis in which 9 psychotherapy research themes emerged, accounting for 60.66% of the variance. Two postsurvey focus groups of clinicians (N = 22) aided in interpreting the findings. The ranking of research themes from most to least important were-Therapeutic Relationship/Mechanisms of Change, Therapist Factors, Training and Professional Development, Client Factors, Barriers and Stigma, Technology and Adjunctive Interventions, Progress Monitoring, Matching Clients to Therapist or Therapy, and Treatment Manuals. Few differences were noted in rankings based on participant age or primary therapeutic orientation. Postsurvey focus group participants were not surprised by the top-rated items, as they were considered most proximal and relevant to therapists and their work with clients during therapy sessions. Lower ranked items may be perceived as externally imposed agendas on the therapist and therapy. We discuss practice research networks as a means of creating new collaborations consistent with KTE goals. Findings of this study can help to direct practitioner-researcher collaborations.

Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions. Thirty-seven participants with treatment-resistant depression (TRD) and baseline SI first received a single ketamine infusion during a randomized, double-blind crossover with midazolam. Following relapse of depressive symptoms, participants received six open-label ketamine infusions administered thrice-weekly over 2 weeks. Antidepressant responders (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] scores) received four further open-label infusions administered once-weekly. Changes in SI were assessed with the suicide items on the MADRS (item 10, MADRS-SI) and the Quick Inventory of Depressive Symptomatology-Self Report (item 12, QIDS-SI). Linear mixed models revealed that compared with midazolam, a single ketamine infusion elicited larger reduction in SI (P = 0.01), with maximal effects measured at 7 days postinfusion (P < 0.001, Cohen's d = 0.83). Participants had cumulative reductions in MADRS-SI scores with repeated infusions (P < 0.001), and no further change with maintenance infusions (P = 0.94). QIDS-SI results were consistent with MADRS-SI. Overall, 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions. This study adds to the growing body of research suggesting ketamine as a possible novel treatment strategy for SI in mood disorders.

Counterirritation, the phenomenon of one painful stimulus reducing pain caused by a second noxious stimulus, has been recognized clinically for decades. Recently a physiological mechanism to explain counterirritation was described and termed diffuse noxious inhibitory controls (DNICs). Nevertheless, few psychophysical studies have examined systematically the effects of a noxious conditioning stimulus on pain perception. The present study examined the perception of painful heat stimuli on the face before, during and after the subject submerged a hand in painfully cold water (5 degrees C) for 5 min (cold pressor pain). We found that the subjects' ratings of the heat stimuli were significantly, although not completely, reduced during the cold pressor pain; this attenuation of pain perception continued after the noxious conditioning stimulus was withdrawn. Similarly, the pain threshold was significantly increased from 45.7 degrees C to 47.3 degrees C while the hand was in cold water and this threshold remained elevated after the cold water was terminated. Since DNICs have been found to completely and selectively inhibit the activity of only one type of pain transmission neuron (wide dynamic range), our data suggest that these neurons are involved in the perception of pain intensity. However, the persistence of residual pain perception in the presence of noxious conditioning stimuli indicates the importance of other nociceptive pathways.

The medial prefrontal cortex has been implicated in pain perception by recent anatomical, physiological, and functional imaging data demonstrating that frontal and anterior cingulate cortices receive inputs related to nociception; neurosurgical case reports suggest that lesions involving these areas may specifically reduce the affective or emotional component of chronic intractable pain. We examined this hypothesis more closely by assessing psychophysical ratings of (1) warmth, pain intensity, and unpleasantness evoked by phasic thermal stimuli, (2) tolerance to tonic cold stimuli, and (3) perceived intensity of visual stimuli, both before and after neurosurgical lesions of the fiber tracts connecting the frontal lobes to subcortical structures. A 22-year-old male, with no history of chronic pain, underwent psychophysical testing 3 days before, 5 days after, and 6 months after receiving bilateral lesions of the anterior internal capsule (aIC), performed as treatment for obsessive-compulsive disorder. In each session, the patient rated the intensity and unpleasantness of 5-sec cutaneous heat stimuli (39-47 degrees C); pain tolerance was measured by means of a cold-pressor test (hand immersion in 1 degrees C water). The patient was able to differentially rate the intensities of heat stimuli during both pre- and postsurgical testing sessions (p < 0.001). However, he rated heat stimuli as less intense 5 days after surgery than during presurgical testing (p < 0.001), with significant decreases in both pain intensity (p < 0.005) and unpleasantness (p < 0.05). Likewise, the patient described the cold-water immersion as less painful following surgery, although his tolerance times were substantially shorter than those of the presurgical evaluation. Ratings of visual stimulus intensity did not differ across the pre- and postsurgical testing periods, suggesting that changes in pain perception were not related to attentional or cognitive deficits. Magnetic resonance imaging 5 days following surgery revealed bilateral lesions and edema centered in the aIC, with some edema in the left frontal lobe. Those 6 months later showed substantially smaller lesions involving less than half of the aIC and no edema; pain ratings and cold-water tolerance measured at that time indicated a substantial return toward the patient's presurgical values. These data suggest that blocking subcortical input to the anterior cingulate and frontal cortices reduces both the perceived intensity and the unpleasantness of noxious stimuli; reduced cold tolerance times--in the face of decreased pain perception--may reflect a disinhibition of cortical control on spinal reflexes.(ABSTRACT TRUNCATED AT 400 WORDS)