Increased Pain Perception Research Articles

Reply to: “Passive smoking increases pain perception in children during invasive medical procedures.”

Reply to: “Passive smoking increases pain perception in children during invasive medical procedures.”

Linkage between increased nociception and olfaction via a SCN9A haplotype.

Background and AimsMutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity.Methods SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14) or rs6746030C>T (R1150W; n = 21) were compared with non-carriers (n = 40). Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli).ResultsThe number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1), 1 allele: 10.6±2.6 (n = 34), 2 alleles: 9.5±2.1 (n = 40)). The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m2, 1 allele: 29.8±10.4 N/m2, 2 alleles: 33.5±10.2 N/m2).ConclusionsThe findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level.

Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission: A role in pain symptom generation?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain. The transient receptor potential vanilloid 1 (TRPV1) channel, which is involved in visceral pain signalling, has been shown to be up-regulated in IBS. Activation of TRPV1 leads to the release of neuropeptides, such as somatostatin and substance P (SP). We hypothesized that increased pain perception in IBS could be explained by increased transcription in TRPV1 and/or altered levels of neuropeptides. We therefore assessed the transcription of TRPV1 and the mucosal concentration of somatostatin and SP in IBS in comparison to healthy volunteers and patients with ulcerative colitis (UC) in remission as disease controls, and to ascertain their relationship to pain symptoms. Sigmoid colonic mucosal samples were collected from 12 patients with IBS, 34 patients with UC in remission and 9 healthy volunteers, in which groups TRPV1 mRNA levels were determined using quantitative polymerase chain reaction and neuropeptide concentrations by radioimmunoassay. Pain symptom intensity was determined by questionnaires. Transcription of TRPV1 as well as the concentration of neuropeptides were significantly higher in IBS, but only the former correlated with pain symptom severity. Increased transcription of TRPV1 may provide a possible explanation for pain generation in IBS. While the neuropeptides SP and somatostatin were both found to be increased in IBS, these changes are not sufficient to explain pain generation. Pain generation in IBS is probably explained by a complex redundancy in the regulation of local nociceptive mechanisms, which remains a subject of intensive investigation.

Effect of Sedation on Pain Perception

Sedation or anesthesia is used to facilitate many cases of an estimated 45 million diagnostic and therapeutic medical procedures in the United States. Preclinical studies have called attention to the possibility that sedative-hypnotic drugs can increase pain perception, but whether this observation holds true in humans and whether pain-modulating effects are agent-specific or characteristic of IV sedation in general remain unclear. To study this important clinical question, the authors recruited 86 healthy volunteers and randomly assigned them to receive one of three sedative drugs: midazolam, propofol, or dexmedetomidine. The authors asked participants to rate their pain in response to four experimental pain tasks (i.e., cold, heat, ischemic, or electrical pain) before and during moderate sedation. Midazolam increased cold, heat, and electrical pain perception significantly (10-point pain rating scale change, 0.82 ± 0.29, mean ± SEM). Propofol reduced ischemic pain and dexmedetomidine reduced both cold and ischemic pain significantly (-1.58 ± 0.28, mean ± SEM). The authors observed a gender-by-race interaction for dexmedetomidine. In addition to these drug-specific effects, the authors observed gender effects on pain perception; female subjects rated identical experimental pain stimuli higher than male subjects. The authors also noted race-drug interaction effects for dexmedetomidine, with higher doses of drug needed to sedate Caucasians compared with African Americans. The results of the authors' study call attention to the fact that IV sedatives may increase pain perception. The effect of sedation on pain perception is agent- and pain type-specific. Knowledge of these effects provides a rational basis for analgesia and sedation to facilitate medical procedures.

Chronic Pain: Fundamental Scientific Considerations, Specifically for Legal Claims

Abstract Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.

Psychiatric morbidity, pain perception, and functional status of chronic pain patients in palliative care

Context:Psychological factors, such as that exist when we experience pain, can profoundly alter the strength of pain perception.Aim:The study aims to estimate the prevalence of psychiatric disorders, and its association with perception of pain and functional status in chronic patients in palliative care.Materials and Methods:The sample was selected via simple randomisation and post consent were assessed using (1) a semi- structured questionnaire to elicit socio-demographic information and medical data (2) Brief Pain Inventory (3) ICD-10 Symptom Checklist (4) ICD-10-Diagnostic Criteria for Research (DCR) (5) Montgomery Asberg Depression Rating Scale (MADRS) (6) Covi Anxiety Rating Scale (7) Karnofsky Performance Status Scale. Data was analysed using independent sample t test and chi square test.Results:The psychiatric morbidity was 67% with depression and adjustment disorders being the major diagnosis. There was a significant association between psychiatric morbidity pain variables (P = 0.000). Psychiatric morbidity significantly impaired activity, mood, working, walk, sleep, relationship, and enjoyment. There was no association between aetiology of pain, type of cancer, treatment for primary condition and treatment for pain and psychiatric morbidity. The functional status of cancer patients was also poorer in patients with psychiatric morbidity (P = 0.008).Conclusion:There is a high prevalence of psychiatric illness in chronic pain patients of any aetiology. Psychiatric morbidity is associated with increased pain perception, impairment in activity and poor functional status.

Does perioperative sleep disruption impact pain perception?

BACKGROUND The typical inpatient hospital experience results in multiple intrusions by hospital personnel, noise, and inadequate treatment of pain that prevents the necessary amount of sleep for hospitalized patients. Sleep disruption results in increased pain perception and lowered pain thresholds. In 1999, the Veterans Health Administration recognized the need to adequately treat pain and began using pain as the fifth vital sign to be recorded at every clinical encounter.

Morphine Induces Hyperalgesia without Involvement of µ-Opioid Receptor or Morphine-3-glucuronide

Opioid-induced hyperalgesia (OIH) is a paradoxical increase in pain perception that may manifest during opioid treatment. For morphine, the metabolite morphine-3-glucuronide (M3G) is commonly believed to underlie this phenomenon. Here, in three separate studies, we empirically assess the role of M3G in morphine-induced hyperalgesia. In the first study, CD-1 mice injected with morphine (15 mg/kg subcutaneously) after pretreatment with the opioid receptor antagonist naltrexone (NTX) (15 mg/kg) showed tail withdrawal latency reductions indicative of hyperalgesia (2.5 ± 0.1 s at t = 30 min, P < 0.001 versus baseline). In these mice, the morphine/M3G concentration ratios versus effect showed a negative correlation (r(p) = -0.65, P < 0.001), indicating that higher morphine relative to M3G concentrations are associated with increased OIH. In the second study, similar hyperalgesic responses were observed in mice lacking the multidrug resistance protein 3 (MRP3) transporter protein (Mrp3(-/-) mice) in the liver and their wild-type controls (FVB mice; latency reductions: 3.1 ± 0.2 s at t = 30 min, P < 0.001 versus within-strain baseline). In the final study, the pharmacokinetics of morphine and M3G were measured in Mrp3(-/-) and FVB mice. Mrp3(-/-) mice displayed a significantly reduced capacity to export M3G into the systemic circulation, with plasma M3G concentrations just 7% of those observed in FVB controls. The data confirm previous literature that morphine causes hyperalgesia in the absence of opioid receptor activation but also indicate that this hyperalgesia may occur without a significant contribution of hepatic M3G. The relevance of these data to humans has yet to be demonstrated.

Obstructive sleep apnoea in relation to rheumatic disease

Sleep problems are common concerns in rheumatology patients and have been independently linked to increased pain perception and fatigue severity. Evidence supports an increased prevalence of primary sleep disorders, including sleep apnoea, in some rheumatic disease populations, particularly RA. Obstructive sleep apnoea is a significant public health concern and contributes to increased cardiovascular morbidity and mortality. Patients with obstructive sleep apnoea have also been found to have elevations in circulating acute-phase markers and pro-inflammatory cytokines. Co-existence of sleep apnoea in rheumatic disease patients may influence the severity of reported symptoms of pain and fatigue, accelerate the risk of cardiovascular events and possibly influence levels of circulating inflammatory markers and mediators. In this article we review the risk factors, prevalence and impact of sleep apnoea from a rheumatological perspective. Additionally, we recommend considering sleep apnoea screening in patients with rheumatic disease and, when appropriate, referral to a specialized sleep disorders clinic.

Mo1848 Characterization of Dorsal Horn Neurons Activated by Noxious Colorectal Distension in Health and Chronic Visceral Hypersensitivity

Background: Little is known about the spinal cord dorsal horn (DH) neurons activated by colonic mechanical stimuli. Even less is known about how chronic hypersensitivity of colonic nociceptors effects DH neuron activity. Methods: Experiments were performed in healthy mice (N=4) and in a TNBS model of post-inflammatory chronic visceral hypersensitivity (CVH; N=4). TNBS (130μL/ml) was administered by colorectal enema and after 28 days mice underwent 80 mmHg of colorectal distension (CRD). By this time inflammation is resolved and the peripheral endings of colonic nociceptors are mechanically hypersensitive1. Following CRD, mice were perfused fixed, spinal cord T10-L1 removed and processed for phosphorylated MAP kinase ERK 1/2 (pERK) immunohistochemistry to identify DH neurons activated by CRD. Spinal sections were co-labeled for calcitonin gene related peptide (CGRP), isolectin B4 (IB4), calbindin, GABA and NMDA receptor subunit 2B (NMDAr2B). The average number of pERK-immunoreactive (IR) neurons from 6-10 spinal sections was compared between healthy and post-inflamed mice using Two-way ANOVA with Bonferroni's posttests whilst unpaired student t-tests determined differences in co-labelling. Results: Significantly more DH neurons were pERK-IR following CRD in CVH mice compared to healthy mice (P<0.0001), specifically in T12-T13 (P<0.05) and T13-L1 (P<0.001). In healthy mice, pERK-IR neurons were located in CGRP-IR laminae I (LI), but not in the IB4-IR substantia gelatinosa. 37±3% of pERK-IR neurons were calbindin-IR, which accounted for 3±0.8% of all calbindin-IR DH neurons, classified as projection neurons in LI and a subtype of excitatory interneuron in LI-LII. All pERK/calbindin-IR neurons were located in LI and NMDAr2B-IR. 3.8±2% of pERK-IR neurons were GABA-IR, which accounted for 0.9±0.6% of all GABAIR DH inhibitory interneurons. In CVH mice, pERK-IR neurons were located in CGRP-IR LI and ventral to the IB4-IR substantia gelatinosa. A smaller proportion of pERK-IR neurons were calbindin-IR (14±5%, P=0.07), which was a consequence of more pERK-IR neurons not containing calbindin-immunoreactivity and the number of pERK/calbindin-IR neurons unchanged. Significantly more pERK-IR neurons were GABA-IR in CVH mice (13.45±3%, P<0.05), with pERK-IR neurons accounting for a greater number of GABA-IR neurons (8±1%, P<0.05). Conclusion: We identified DH neurons responsive to colonic mechanical stimulation. We also show that the chronic hypersensitivity of colonic afferent endings following inflammation leads to a significant increase in the number of DHneurons responsive to noxious colonic stimulation. These data also indicate a change in the types of DH neurons activated by colonic mechanical stimuli post-inflammation. Such DH changes may correlate with increased pain perception associated with CVH. 1) Hughes & Brierley, et al. Gut. 2009.

Altered brain activation to colorectal distention in visceral hypersensitive maternal‐separated rats

Early life trauma can predispose to increased visceral pain perception. Human neuroimaging studies emphasize that altered brain processing may contribute to increased visceral sensitivity. The aim of our study was to evaluate brain responses to painful visceral stimuli in maternal-separated rats before and after acute stress exposure in vivo. H(2)(15)O microPET scanning was performed during colorectal distention in maternal-separated rats before and after water avoidance stress. Brain images were anatomically normalized to Paxinos space and analyzed by voxel-based statistical parametric mapping (SPM2). Colorectal induced visceral pain was assessed by recording of the visceromotor response using abdominal muscle electromyography. Colorectal distention (1.0-2.0 mL) evoked a volume-dependent increase in visceromotor response in maternal-separated rats. Stress [water avoidance (WA)] induced an increased visceromotor response to colorectal distention in awake and anesthetized rats. In pre-WA rats, colorectal distention evoked significant increases in regional blood flow in the cerebellum and periaquaductal gray (PAG). Colorectal distention post-WA revealed activation clusters covering the PAG as well as somatosensory cortex and hippocampus. At maximal colorectal distention, the frontal cortex was significantly deactivated. WA stress induced increased pain perception as well as activation of the somatosensory cortex, PAG, and hippocampus in maternal-separated rats. These findings are in line with human studies and provide indirect evidence that the maternal separation model mimics the cerebral response to visceral hypersensitivity in humans.

P-118 - Anxiety increased perioperative pain perception in children

Children undergoing surgery experience show presurgical anxiety high levels. Our aim was to examine the relationship between perisurgery anxiety and pain perception in children. Methods An observational prospective study in children ( Results 319 children 4.4 ± 0.2 years old (85 female 5.5 ± 0.4 years old, 234 male 4.1 ± 0.2 years old) were enrolled. The surgery procedures were hernia repair (40.4%) followed by dermatologic extirpations (12.5%), and appendicectomies (9.7%). A 79% of the patients had general anaesthesia and 16.9% had locorregional-general anaesthesia. In PARU: 9.1% of the patient received analgesia: ketorolac 5.3%, metamizol 2.2%, other NSAIDs 6.3%, opioids 1.8%, benzodiazepines 2.2%, NSAIDs+opioids+benzodiazepines 0.3%). In ODU: 47% of the patient received analgesia (ibuprofen 39.5%, paracetamol 7.6%, metamizol 2.8%). In 24 hU: 50.2% of the patient received analgesia: metamizol 27%, ibuprofen 16%, paracetamol 3.4%, ketorolac 0.6%, opioids 1.2%, benzodiazepines 0.3%, NSAIDs+paracetamol 0.9%, NSAIDs+opioids+benzodiazepines 0.6%, NSAIDs+opioids+ antiemetics 4.7%, elastomers 4.7%. Total medium AVS were (% of increment vs. pre-surgery): pre-surgery 0.89 ± 0.1 Conclusion Perisurgery anxiety increase pain perception leading an increased analgesic consumes in children.

Increased pain perception and attenuated opioid antinociception in paradoxical sleep-deprived rats are associated with reduced tyrosine hydroxylase staining in the periaqueductal gray matter and are reversed by L-DOPA

Paradoxical sleep deprivation (PSD) increases pain sensitivity and reduces morphine antinociception. Because dopaminergic neurons in the periaqueductal gray matter (PAG) participate in pain modulation and opioid-induced antinociception, we evaluated the effects of PSD on thermal pain sensitivity, morphine- and L-DOPA-induced antinociception and dopaminergic functionality in the PAG by assessing tyrosine hydroxylase (TH) immunoreactivity. Rats that were subjected to 96h of PSD received vehicle, morphine (2.5, 5 or 10mg/kg), L-DOPA (50 or 100mg/kg) or L-DOPA (50mg/kg)+morphine (2.5 and 5mg/kg) and were tested with a 46°C hot plate 1h after. The paw withdrawal latency responses to the hot plate were decreased in PSD rats and were modified by the highest dose of morphine, L-DOPA and L-DOPA+morphine. Analgesic effects were observed in control groups for all of the morphine doses as well as 100mg/kg of L-DOPA and L-DOPA (50mg/kg)+morphine (5mg/kg). The number of cell bodies that were immunopositive for TH in the PAG was reduced in PSD rats. In conclusion, increased thermal sensitivity was reversed by L-DOPA and could be caused by a reduction TH levels in the PAG. Our data also suggest a relationship between central dopaminergic networks and opiate-induced analgesia in rats.

S34-01 - Putative cerebral correlates of abberant pain processing in depression

The complex sensory experience of pain involves cognitive, behavioural and emotional aspects which are closely interrelated. While patients suffering from major depressive disorder (MDD) mainly exhibit increased thresholds towards experimentally induced thermal pain applied to the skin, the induction of sad mood increases pain perception in healthy controls.Neurobiological underpinnings of the discrepancy of pain perception in depression and after sad mood induction in healthy volunteers will help to understand aberrant pain perception in the disease. Patients and controls were rated on mood scales and results were correlated to brain activity assessed in fMRI sessions. Similarly, autonomic modulation in respect to pain perception was assessed in patients.We found a highly significant reduction in heat pain threshold on the left hand after sad mood induction in patients and controls. Subjects were scanned twice, one group before and after sad-mood induction and another group before and after neutral-mood induction, respectively. Our main finding was a significant group×mood induction interaction bilaterally in the ventrolateral nucleus of the thalamus indicating a BOLD signal increase after sad-mood induction and a BOLD signal decrease in the control group.We present evidence that induced sad affect leads to reduced heat pain thresholds in healthy subjects and depressed patients. This is probably due to altered lateral thalamic activity, which is potentially associated with changed attentional processes. Furthermore we present evidence for similar changes in depressed patients after sad mood induction. Autonomic modulation is less likely to interfere with pain perception in the disease.

Does intraoperative remifentanil infusion really make more postoperative pain?

Does intraoperative remifentanil infusion really make more postoperative pain?

Gender Variation In Pain Perception After Intravenous Cannulation In Adults

Intravenous cannulation is the most frequently used procedures in the wards, casualty and in preoperative preparation. It is a very painful and stressful procedure, thus emotions may become exaggerated at times, triggering vasovagal reaction. Patient’s anxiety and fears concerning needles are real and may even prevent them from seeking health care.Our Aim was to estimate the level of pain perception after intravenous cannulation using Visual analogue pain scale among adult males and females and to study the gender variation in perception of pain.The study was conducted after ethical clearance, with a total of 100 subjects, informed consent was taken. Immediately after the intravenous cannulation using 20 gauge intravenous cannula the subjective pain was assessed by using Visual Analogue pain scale (VAS) on 0 (No pain) – 10 (Max pain). Results thus obtained were analyzed by Pearson Chi Square test(X).Pain perception was moderate to severe (5-10) in 64% of females as compared to 12% in males. There was significant increase in pain perception in females compared to males (X = 31.84, p<.001). BACKGROUND Pain is one of the most common widely under-treated health problems. As a basic scientific definition, pain is a sensation caused by some type of noxious stimulus. From the behavioural aspect, pain is a pattern of responses that function to protect an individual from harm. The International Association for the Study of Pain (IASP) defines pain as “an unpleasant, subjective sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Untreated and inadequately treated pain causes suffering. Almost every tissue found in the human body contains pain receptors, called nociceptors. It has been estimated that the skin may contain as many as 1,300 nociceptors in one square inch. These nociceptors respond to thermal, chemical, and mechanical stimuli through a-delta, C, and a-beta fibres. The a-delta receptors contain small, myelinated fibres that rapidly transmit acute, sharp pain signals from the peripheral nerves to the spinal cord. C receptors have larger, unmyelinated fibres that transmit pain at a slower rate and are commonly associated with long lasting, burning pain sensation. Intravenous cannulation is the most frequently used procedure in the wards, casualty and in preoperative preparation. It is a very painful and stressful procedure, thus emotions may become exaggerated at times, triggering vasovagal reaction. Patient’s anxiety and fears concerning needles are real and may even prevent them from seeking health care. AIMS & OBJECTIVES To estimate the level of pain perception after intravenous cannulation using Visual analogue pain scale among adult males and females. To study the gender variation in perception of pain. METHODS AND MATERIALS The study was conducted with a total of 100 subjects, after obtaining Ethical clearance and informed consent. The age group included 18 to 50 years of either sex and subjects were taken from general wards and preoperative wards. Immediately after the intravenous cannulation by a trained person, with a single attempt, using 20 gauge IV cannula, the subjective pain was assessed by asking the person to give a score depending on the intensity of pain he/she experienced during cannulationusing Visual Analogue pain scale (VAS) on 0 (No pain) – 10 (Max pain).In case of illiterate patients the Faces of pain scale was used and 05 scale was doubled to match the VAS scores. Gender Variation In Pain Perception After Intravenous Cannulation In Adults 2 of 4 Results thus obtained were analyzed by Pearson Chi Square test (X). Figure 1 The Faces of Pain Scale

Enhanced Central Thermal Nociception in Mildly Depressed Nonpatients and Transiently Sad Healthy Subjects

Evidence of support for sensory changes during minor depression and sadness is scarce and the neural mechanisms are unclear. We assessed central pain processing engaged in nociceptive C-fiber polymodal activity by examining the perception of a non-noxious unpleasant burning sensation induced by a thermal grill illusion, in 26 nonpatients with minor depression (19 females) and 28 healthy subjects (18 females), between 19 and 61 years old and pain free at the study. Controls were also subjected to induction of transient moods. Subjects with depression reported increased pain perception; this increase was more pronounced for the affective dimension of pain (unpleasantness) than for its sensory dimension (intensity). The perception of pain unpleasantness, pain intensity, and overall pain showed positive and linear correlations with depression levels measured by Zung's and Beck's scales. In controls, sad mood induction only increased the scores assigned to negative mood-describing adjectives; the perception of pain intensity, unpleasantness, and overall pain were significantly increased following sad, but not neutral or elevated, mood inductions. Yet, pain intensity and unpleasantness were correlated linearly and reciprocally to positive, instead of negative, mood-describing adjective scores. Thus, there is a central thermal hyperalgesia in subjects with minor depression and sadness. There is a central thermal hyperalgesia in subjects with minor depression, probably associated with an enhanced central processing of nociceptive C-fiber polymodal activity at anterior cingulate cortex, that is predominately expressed as an increased unpleasantness and that could be in part counteracted by behavioral therapies leading to mood elevation.

Effects of Paired-pulse Transcranial Magnetic Stimulation of the Motor Cortex on Perception of Experimentally Induced Pain

We investigated the influence of paired-pulse transcranial magnetic stimulation (ppTMS) of the motor cortex (M1) on perception of noxious electrical stimuli. The nociceptive flexion reflex response was assessed to determine spinal effects. In the first experiment, the effect of ppTMS of M1 on perception of noxious stimulation of the sural nerve was assessed by varying the stimulus onset asynchronies (SOAs) and the order of the stimulations (-400, -75, -25, 25, 125, 400 ms and control ppTMS, negative sign: ppTMS precedes the noxious stimulation). Effects of a preceding ppTMS on the RII and the RIII response of the nociceptive flexion reflex were investigated for SOAs of -400 and -75 ms. The effects of ppTMS of M1 and of the occipital cortex (Oz) on noxious stimulation of the radial nerve were investigated in a second experiment. Visual analogue scales were used to assess pain intensity and unpleasantness. The results revealed increased pain unpleasantness scores for SOAs of -75, -25, 25, and 400 ms and decreased pain intensity scores for a SOA of -400 ms, when the sural nerve and M1 were stimulated. An increase of the area of the RII response was found for a SOA of -75 ms. For stimulation of the radial nerve, ppTMS of Oz but not of M1 increased the perceived pain at a SOA of 25 ms. The facilitatory component of ppTMS led to increased pain perception when applied during the cortical process of Adelta fiber-mediated input, whereas the subsequent inhibitory component may lead to the opposite effect on the subsequent noxious stimulation.

Flexible Cerebral Connectivity Patterns Subserve Contextual Modulations of Pain

The perception of pain can be significantly modulated by the behavioral context. Here, we investigated how contextual modulations of pain are subserved in the human brain. We independently modulated the attentional and emotional context of painful stimuli and recorded brain activity by using functional magnetic resonance imaging. Our results confirm that attention to pain and a negative emotional context increases pain perception and this is concomitantly associated with increased neural activity in the anterior insular cortex. Connectivity analyses further reveal that during attentional and emotional modulations of pain, the anterior insula selectively and flexibly connects to attentional and emotional brain networks in frontoparietal and medial temporal lobe areas, respectively. We conclude that the flexible functional connectivity of the anterior insula to other functional systems of the brain, for example, attentional and emotional brain networks, subserves the extraordinary sensitivity of the pain experience to contextual modulations.

Chronische Schmerzen nach Operationen – Pathophysiologie und prädisponierende Faktoren

Chronic postoperative pain is a most serious, unrecognized problem. Acute postoperative pain can be viewed as the initial step of an extensive, persistent nociceptive and behavioural cascade triggered by tissue and nerve injury. As a result, neuronal plasticity in all parts of the nociceptive system leads to an increase in pain perception. In most patients, chronic postoperative pain resembles neuropathic pain, occasionally however, pain is caused by continuous inflammatory responses. Identification of the etiology of pain is essential for its successful treatment. Both postoperative pain and the risk for the development of chronic postoperative pain are determined by preoperative, intraoperative, and postoperative factors. To identify the contribution of relevant determinants and modulators of postoperative pain, large prospective controlled clinical studies are urgently required that include measurement and documentation of all risk factors and procedure-specific aspects.