Preoperative preemptive drug administration for acute postoperative pain: A systematic review and meta-analysis.

Preoperative administration of pharmacological substances, such as non-steroidal anti-inflammatory drugs or opioids, has been gaining acclaim as a preemptive measure to minimize postoperative pain. This systematic review and meta-analysis aimed at evaluating the effectiveness of this approach in adults undergoing surgical procedures. MEDLINE, EMBASE and the Cochrane Central Register were searched from inception through January 2015. Data from randomized placebo-controlled trials were screened, extracted and assessed for risk of bias according to The Cochrane Collaboration's Tool by two independent authors. The primary outcome measure was reduction in postoperative analgesic consumption during 24 h post surgery; effects were described as mean differences between the drug and placebo arms with corresponding 95% confidence intervals (CIs) and were pooled using random-effects models. Potential publication bias was tested using funnel plots and Egger's regression test for funnel plot asymmetry. Screened were 511 records, of which 39 were included in the final synthesis with data from 3172 patients. A significant reduction in postoperative analgesic consumption was observed using preoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs; 95% CI, -0.61 to -0.14; 31 comparisons), chiefly by the COX-2 inhibitors class (95% CI, -0.95 to -0.33; 13 comparisons). Significant reduction was also observed for gabapentin (95% CI, -1.60 to -0.38; 6 comparisons). No significant effects were observed using opioids, propionic acids or oxicam derivatives. WHAT DOES THIS REVIEW ADD?: Current analyses endorse the effectiveness of COX-2 inhibitors and gabapentin in reducing acute postoperative pain when administered preemptively presurgery. Such corroboration is not found for opioids and other NSAID classes.

A novel electroencephalography-based tool for objective assessment of network dynamics activated by nociceptive stimuli.

BACKGROUND: Pain perception is typically assessed using subjective measures; an objective measure of the response to pain would be valuable. In this study, Brain Network Activation (BNA), a novel multivariate pattern analysis and scoring algorithm, was applied to event-related potentials (ERPs) elicited by cortical responses to brief heat stimuli. Objectives of this study were to evaluate the utility of BNA as a quantitative and qualitative measure of cortical response to pain. METHODS: Contact Heat Evoked Potentials (CHEPs) data were collected from 17 healthy, right-handed volunteers (10 M, 7F) using 5 different temperatures (35, 41, 46, 49 and 52 °C). A set of spatio-temporal activity patterns common to all the subjects in the group (Reference Brain Network Model; RBNM) was generated using the BNA algorithm, based on evoked responses at 52 °C. RESULTS: Frame by frame 'unfolding' of the brain network across time showed qualitative differences between responses to painful and non-painful stimuli. Brain network activation scores were shown to be a better indicator of the individual's sensitivity to pain when compared to subjective pain ratings. Additionally, BNA scores correlated significantly with temperature, demonstrated good test-retest reliability, as well as a high degree of sensitivity, specificity and accuracy in correctly categorizing subjects who reported stimuli as painful. CONCLUSIONS: These results may provide evidence that the multivariate analysis performed with BNA may be useful as a quantitative, temporally sensitive tool for assessment of pain perception.

'Virtual lesion' in pain research; a study on magnetic stimulation of the primary motor cortex.

BACKGROUND: 'Virtual lesion' ('VL') is a transient disruption of cortical activity during task performance. It can be induced by single pulses or short trains of transcranial magnetic stimulation (TMS) directed to functionally relevant brain areas. We applied 'VL' methodology of a short train of TMS given on top of experimental tonic pain, expecting to see changes in pain scores. METHODS: Thirty young healthy subjects (15 women) were assessed with active ('VL') or 'sham' TMS in different sessions, randomly. In each session, 30 sec-long contact heat (47.5 °C, right forearm) was applied stand-alone ('baseline') and with 5 sec-long 10 Hz-TMS over left primary motor cortex (M1) starting at 17 sec of the heat stimulation. RESULTS: Pain scores decreased after 'VL' or 'sham' (p < 0.001). Independently of the type of TMS, pain reduction was stronger in women (p = 0.012). A triple Sex x Stimulation type ('VL' or 'sham') x Condition ('baseline' heat pain vs. heat pain with TMS) interaction (p = 0.027) indicated stronger pain reduction by 'VL' in women (p = 0.008) and not in men (p = 0.78) as compared to 'baseline'. Pain catastrophizing and perceived stress ratings affected the model (p = 0.010 and p < 0.001, respectively), but without sex differences. CONCLUSIONS: This study indicates that interactions between cortical excitability of the motor cortex and nociceptive processing may be gender-related.

Recommendations on practice of conditioned pain modulation (CPM) testing.

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results.

Atypical central pain processing in sensory modulation disorder: absence of temporal summation and higher after-sensation.

Sensory over-responsivity (SOR), a subtype of the proposed sensory modulation disorder (SMD), is characterized by over-responsiveness to stimuli in several sensory modalities. SMD individuals demonstrate abnormal responses to naturally occurring stimuli in a manner that interferes with daily life participation. Previous psychophysical testing of the somatosensory system revealed that SOR individuals rated pain sensations higher than controls, demonstrating hyperalgesia that can be centrally mediated. Temporal summation (TS) of second pain and after-sensation are manifestations of central sensitization; therefore, this study explored these measures for better characterization of central pain processing in SOR. Twelve SOR adults and 12 healthy controls participated. TS was produced by a train of fifteen repetitive heat pulses, 0.7 s duration each, and 2 s of inter-stimulus interval, applied to the thenar-eminence, while four pain ratings were obtained. An after-sensation was then measured for 5 min, obtaining six pain ratings. No TS of pain was indicated in the SOR group (SOR: p = 0.36; control: p < 0.001). Further, while controls reported a gradual disappearance of pain after-sensation, individuals with SOR continued to report pain for the duration of the 5 min measured (p = 0.002). These results demonstrate an atypical response pattern, suggesting alteration in pain processing and/or modulation at a central level in individuals with SOR. These possible neural changes may manifest themselves as interference with daily functioning as well as shed light on some of the between-subject variability seen in psychophysical testing in non-painful subjects.

Associations between autonomic dysfunction and pain in chemotherapy-induced polyneuropathy.

BACKGROUND: Autonomic neuropathy, a relatively common complication of several chemotherapy agents, can affect the vagus nerve and its pain inhibitory capacity, thus increasing sensitivity to pain. This study aimed to evaluate the relationships between autonomic parasympathetic function and the perception of (1) spontaneous pain; (2) experimental non-painful sensations; and (3) experimental painful sensations in chemotherapy-induced neuropathy patients. METHODS: Twenty-seven cancer patients with chemotherapy-induced polyneuropathy were enrolled (20 women, age 56.6 ± 7.9). Autonomic parameters of heart rate variability, deep-breathing and Valsalva ratios, experimental non-painful parameters of warm, cold and mechanical detection thresholds, and painful parameters of heat pain thresholds, pain rating of suprathreshold stimulus, mechanical temporal summation and conditioned pain modulation response were examined. RESULTS: Autonomic parameters and spontaneous pain levels were not associated, yet autonomic parameters were positively correlated with non-painful sensations - milder autonomic neuropathy was accompanied by milder sensory neuropathy as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher warmth detection threshold (r = -0.465; p = 0.033). Autonomic parameters were, however, negatively correlated with painful sensations - lower parasympathetic-vagal activity was associated with higher pain sensitivity as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher pain rating of suprathreshold stimulus (r = -0.559; p = 0.008). CONCLUSIONS: Diminished vagal function due to neuropathy is associated with, and may possibly underlie, pain disinhibition expressed as greater levels of experimental pain.

Asymmetric pain processing in Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. METHODS: Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. RESULTS: An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. CONCLUSIONS: Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD.

Pretreatment with aspirin and etiology of first-ever ischemic stroke in young and middle-aged patients.

BACKGROUND: There are very limited data on the influence of pretreatment with aspirin (ASA) on the etiology of subsequent first-ever ischemic stroke. MATERIALS AND METHODS: Five hundred ninety eight patients 65 years old or younger with first-ever ischemic stroke either pretreated (N=167) or not treated with aspirin (N=431) participated. RESULTS: The mean age was 56.5+/-6.0 years for patients treated with ASA and 53.1+/-8.9 years for those not treated (p<.0001). All major vascular risk factors except smoking were significantly more frequent among the patients pretreated with aspirin. Logistic regression analysis adjustments for age, gender, and major vascular risk factors revealed an overall significant effect (p<0.0001) of aspirin treatment on the distribution of stroke etiologies. Subsequent separate analyses on stroke etiology subtypes indicated that the incidence of small vessel disease (SVD) related strokes was significantly reduced by pretreatment with aspirin (OR=0.63). Logistic regression analysis showed no influence of aspirin on the likelihood of a favorable or unfavorable outcome, as expressed by Rankin scale. CONCLUSION: Pretreatment with ASA has significant influence on the distribution of etiologies of first-ever ischemic stroke in young and middle-aged patients, when the immediate functional stroke outcome is not influenced by ASA pretreatment.

Size of PFO and amount of microembolic signals in patients with ischaemic stroke or TIA.

BACKGROUND AND PURPOSE: The inter-relation between the size of patent foramen ovale (PFO) by transesophageal echocardiography (TEE) and the amount of microembolic signals (MES) on transcranial doppler (TCD) is still not determined. METHODS: The study group comprised of 104 patients with first-ever ischaemic stroke or transient ischemic attack (TIA). Three groups were formed according to the amount of MES on TCD: a small amount of MES (0-10 MES); a moderate amount of MES (countable MES higher than 10); and multiple MES. RESULTS: According to TEE, there were 52 patients (50%) with a small PFO, 37 patients (35.6%) with a moderate PFO, and 15 patients (14.4%) with a large PFO. There were 48 patients (46.1%) with a small amount of MES, 34 patients (32.7%) with a moderate amount of MES, and 22 patients (21.1%) with multiple MES on TCD. A strong relationship between the size of the PFO on TEE and the amount of MES on contrast transcranial Doppler was found (P < 0.0001), such that the larger the PFO on TEE, the greater the amount of MES on TCD. CONCLUSIONS: There is a high correlation between the size of the PFO on TEE and the amount of MES on TCD in stroke and TIA patients.

Countable and non-countable microembolic signals by TCD in first-ever stroke or TIA patients with PFO.

BACKGROUND: There are data in the literature indicating that the number of microembolic signals (MES) in patients with patent foramen ovale (PFO) is directly related to stroke incidence and recurrence. We thus hypothesized that the amount of artificially induced microembolic signals monitored by contrast transcranial Doppler (cTCD) would be greater in younger patients with PFO and stroke (when cryptogenic strokes related to the PFO are frequent). PATIENTS AND METHODS: The final analysis included 109 patients with first-ever ischemic stroke or TIA with PFO, as detected by Transesophageal Echocardiography (TEE), and MES, as measured by cTCD. Thirty-seven patients (aged 19-45 years) were defined as the "younger" group, and the other 72 patients (aged 46-77 years) were defined as the "older" group. Eighty-six patients (78.9%) suffered from stroke, including 28 in the younger group and 58 in the older group. The pattern of microembolization was defined as "countable" when the observers were able to calculate the number of MES. In the case of a "shower" of MES on TCD examination, the pattern of monitoring was defined as "non-countable." RESULTS: Ischemic heart disease, and hyperlipidemia were found to be significantly more frequent in the group of older patients. Twenty-three patients (62.2%) in the younger group had cryptogenic stroke or TIA (no risk factors found), as compared to 26 patients (36.1%) in the older group (p=0.009). There were 23 patients with a non-countable pattern of MES in the older group, as compared with 5 such patients in the younger group (p=0.04). There was no difference found in the number of MES between the groups in those patients with a countable pattern of MES (13.3+/-11.8 in the younger group vs. 13.7+/-11.7 in the older group). CONCLUSIONS: In stroke and TIA patients above 45 years of age, PFOs producing a large amount of MES on TCD examination are frequent. Thus, there is no correlation between a large amount of MES and stroke or TIA in young patients.

Distribution of etiologies in patients above and below age 45 with first-ever ischemic stroke.

BACKGROUND: There is limited information about distribution of etiologies of ischemic stroke in different age groups. MATERIALS AND METHODS: In this study, we applied the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification in 87 patients aged < or = 45, and in 347 patients aged 46-60 years with first-ever ischemic stroke in order to follow the distribution of stroke etiologies in different age groups. RESULTS: Traditional risk factors, except smoking and atrial fibrillation, were more frequent in older patients. The most frequent etiologies in the younger stroke patients (aged < or = 45) were 'other' than routine causes (26.4%), cardioembolism (22.4%) and 'idiopathic' strokes (20.7%), when no cause was found. In older patients (aged 46-60), small vessel disease (25.1%) and cardioembolism (22.2%) were the most frequent etiologies of stroke. CONCLUSIONS: In stroke patients below the age of 45, the TOAST classification should be expanded to better classify the wide diversity of stroke etiologies. The relatively low frequency of routine stroke etiologies in patients aged < or = 45 can be explained by the significantly lower prevalence of traditional risk factors in these patients. In patients 46-60 years old, the TOAST classification is adequate in the characterization of ischemic stroke etiologies.

Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial.

In order to define the impact of needle type on post-lumbar puncture headache (PLPH), we performed a prospective, randomized trial comparing the incidence of PLPH in patients undergoing lumbar punctures (LPs) with traumatic vs atraumatic 22-gauge needles. Fifty-eight patients underwent 85 LPs. The incidence of PLPH was 36% in the traumatic vs 3% in the atraumatic group (p = 0.002).

Cerebral hemodynamics in symptomatic and asymptomatic patients with severe unilateral carotid stenosis before and after carotid endarterectomy.

BACKGROUND: Data concerning hemodynamic status prior to and after carotid endarterectomy (CEA) in symptomatic and asymptomatic patients is insufficient. Transcranial Doppler (TCD) provides information regarding compensatory collateral flow as well as mechanisms of cerebral autoregulation in patients with carotid stenosis. PATIENTS AND METHODS: Forty eight symptomatic and 81 asymptomatic patients with unilateral severe carotid stenosis were examined by TCD before and in early postoperative period after CEA. RESULTS: Cigarette smoking was the only risk factor significantly more frequent in symptomatic patients. Preoperative anterior cerebral artery (ACA) and middle cerebral artery (MCA) asymmetry, basilar artery velocity and number of ophthalmic arteries with reversed flow, were not significantly different between the two groups. Pulsatility index, cerebrovascular reactivity and flow acceleration on the side of stenosis were significantly lower in symptomatic patients. After surgery there was a significant improvement of all TCD parameters in symptomatic as well as asymptomatic patients. CONCLUSIONS: The exhausted ability of cerebral autoregulation is an important factor differentiating between symptomatic and asymptomatic patients with severe carotid stenosis. Successful surgery provides good recovery of cerebral hemodynamics in both symptomatic and asymptomatic patients.

Quantitative measurement of pain sensation in patients with Parkinson disease.

BACKGROUND: Pain is common in patients with Parkinson disease (PD) and can precede the diagnosis of the disease. Experimental studies and clinical evidence indicate involvement of basal ganglia and dopaminergic pathways in central pain processing. OBJECTIVE: To quantitatively assess and compare pain perception in patients with unilateral PD with and without pain and in patients with response fluctuations. METHODS: Thirty-six patients with PD (mean age, 61.8 +/- 11.2 years) with predominantly unilateral disease, 15 patients with response fluctuations (mean age, 65.3 +/- 10.4 years), and 28 age-matched healthy control subjects participated in the study. Subjective pain was assessed using the visual analog scale with von Frey filaments for tactile thresholds and contact thermode for warm sensation (WS) and heat pain thresholds (HPTs). RESULTS: Tactile and WS thresholds did not differ between patients in both patient groups and control subjects nor between sides. HPT was lower in patients with PD who experienced pain (n = 21) compared with those who did not (42.6 +/- 3.0 degrees C vs 45.6 +/- 2.8 degrees C; p < 0.01) and those who experienced pain in the more affected side (41.4 +/- 2.6 degrees C vs 43.7 +/- 3.3 degrees C; p < 0.0001). In patients with fluctuations there were no side differences in WS and HPT or between "on" and "off" periods. CONCLUSION: Endogenous pain in patients with Parkinson disease is accompanied by increased sensitivity to some painful stimuli, suggesting that basal ganglia abnormality also involves pain encoding.

Assessment of ophthalmic artery collateral pathway in the hemispheric cerebral hemodynamics in patients with severe unilateral carotid stenosis.

The role of ophthalmic artery collateral pathway in hemispheric hemodynamics in patients with severe carotid stenosis is controversial. The aim of the present study was to address this question comparing the asymmetry of the velocity in middle and anterior cerebral arteries (MCAs and ACAs) and cerebrovascular reactivity (CVR) in MCA on stenotic side in the patients with unilateral severe stenosis of internal carotid artery (ICA) in patients with and without ophthalmic artery collateral pathway. The cohort of 118 patients with carotid stenosis was prospectively assembled. Fifty patients who had severe unilateral ICA stenosis (71%-99%) by Duplex Ultrasound (DUS) were observed by transcranial Doppler (TCD). Cerebral blood flow velocity in MCA and ACA in both sides, direction of blood flow in ophthalmic artery (OA) and CVR on the side of stenosis were determined. There were 14 patients with retrograde blood flow in OA (Group I). The remaining 36 patients with anterograde flow in OA composed Group II. The degree of interarterial asymmetry of peak and mean velocity (Vpeak and Vmean) in MCA and ACA and CVR in MCA were compared in both groups. The degree of ACA asymmetry by Vpeak was 44.0% +/- 6.9% in Group I and 38.3% +/- 3.9% in Group II (p = 0.49), by Vmean 40.3% +/- 6.7% and 36.6% +/- 3.8% (p = 0.63) respectively. The degree of MCA asymmetry by Vpeak was 24.2% +/- 2.8% in Group I and 19.5% +/- 5.0% in Group II (p = 0.42), by Vmean 23.5% +/- 2.9% and 20.6% +/- 5.1% (p = 0.63) respectively. CVR in Group I was 26.1% +/- 6.1%, in Group II 29.0% +/- 6.7% (p = 0.65). The ophthalmic collateral pathway has no influence on hemispheric cerebral hemodynamics in patients with severe unilateral carotid stenosis.

The nature of microemboli in patients with artificial heart valves.

Cognitive decline has recently been found to be associated with microemboli in cerebral vessels in patients with artificial heart valves. The authors sought to determine the nature of such microemboli, that is, whether they are gaseous or solid, by comparing their characteristics to those of artificially generated air emboli in patients with patent foramen ovale (PFO). Three hundred and forty-eight microemboli were recorded in 11 patients with artificial valves (all taking coumadin), and 86 microemboli were recorded in response to intravenous injection of saline agitated with air in 8 PFO patients. No difference in intensity, duration, or relative velocity of microemboli was found between groups. The authors conclude that microemboli generated from artificial heart valves are generally gaseous and not solid.

The assessment of radiating low back pain by thermal sensory testing.

Low back pain radiating into the legs is a common pain syndrome. However, neurological examination, imaging and electromyographic studies are of limited value for prognosis or therapy. The origin of the pain remains unknown. The aim was to evaluate the potential of thermal sensory testing to serve as a diagnostic tool in 24 patients who had low back pain radiating down the S1 dermatome, compared with 26 pain-free controls. The method of limits was used to detect the thresholds of warm sensation, cold sensation, warm pain and cold pain at the L4, L5 and S1 dermatomes of the symptomatic and the non-symptomatic legs. Thresholds on the asymptomatic leg were similar to values obtained in controls. We found a significantly higher threshold for cold sensation in the S1 dermatome of the symptomatic leg of the patients compared with the controls (p< 0.005). In addition, patients who had abnormal neurological examination (50%) had higher thresholds for cold sensation or cold pain in the three dermatomes tested at the symptomatic leg compared with the non-symptomatic leg. No differences in the thresholds of warm sensation or warm pain were detected. We propose that these findings indicate selective damage to the Adelta fibres which are involved in transmission of cold sensation and pain, presumably by root compression. We found no evidence of involvement of C fibres, which transmit warm sensation and pain. Thermal testing should be considered among the testing modalities that are capable of demonstrating objective findings in patients with radiating low back pain.

Simultaneous recording of late and ultra-late pain evoked potentials in fibromyalgia.

OBJECTIVE: To characterize laser evoked potentials (LEP), pain psychophysics and local tissue response in fibromyalgia patients. METHODS: LEP were recorded in 14 women with fibromyalgia in response to bilateral stimulation of tender and control points in upper limbs by 4 blocks of 20 stimuli at each point. Subsequently, heat pain thresholds were measured and supra-threshold magnitude estimations of heat pain stimuli were obtained on a visual analogue scale. Finally, the extent of the local tissue response induced by the previous stimuli was evaluated. RESULTS: Laser stimuli elicited two long latency waves: A late wave (mean latency 368.9+/-66.9 ms) in most patients (13/14) from stimuli at all points, and an ultra-late wave (mean latency 917.3+/-91.8 ms) in 78.5% of the patients at the control points and in 71.4% at the tender points. Amplitude of ultra-late waves was higher at the tender points (20.67+/-11.1 microV) than at the control points (10.47+/-4.1 microV) (P=0.016). Pain thresholds were lower in the tender (41.2+/-2.7 degrees C) than the control points (43.9+/-3.2 degrees C) (P=0.008). Local tissue response was significantly more intense at tender than control points (P=0.004). CONCLUSIONS: Ultra-late laser evoked potentials can be recorded simultaneously with late potentials. Our findings are compatible with presence of peripheral C-fiber sensitization, mostly at tender points, probably combined with generalized central sensitization of pain pathways in fibromyalgia.

Pain perception in women with dysmenorrhea.

OBJECTIVE: To determine if systemic processing of pain differs in women with and without dysmenorrhea. METHODS: Twenty-two dysmenorrheic women and 31 nondysmenorrheic women were studied by pain threshold and supra-threshold magnitude estimation to heat stimuli, pain-evoked potentials by laser stimuli, and anxiety scores four times across their menstrual cycles. RESULTS: Significant differences were found between dysmenorrheic and nondysmenorrheic women. In all four examinations across the menstrual cycle, dysmenorrheic women had longer latencies of pain-evoked potentials (383.08 +/- 6.8 msec versus 345.05 +/- 7.0 msec, P <.001), higher magnitude estimations on visual analog scale of supra-threshold pain (83.29 +/- 2.87 versus 63.50 +/- 3.82, P <.001), and higher state anxiety scores (37.69 +/- 1.7 versus 29.20 +/- 1.9, P =.002). CONCLUSION: Women with dysmenorrhea show enhanced pain perception compared to nondysmenorrheic women. This augmentation of pain perception may be part of the development of dysmenorrhea.