Repetitive noxious stimuli during early development affect acute and long-term mechanical sensitivity in rats.

BACKGROUND: Prematurely born infants are frequently exposed to painful procedures in the neonatal intensive care unit, causing changes to the development of the nervous system lasting into adulthood. The current study aims to study acute and long-term consequences of neonatal repetitive noxious stimulation. METHODS: Rat pups received either 4 or 10 unilateral needle pricks per day, while control littermates received 4 or 10 tactile stimuli in the first postnatal week. Behavioural sensitivity was assessed in the neonatal phase, in adulthood, and after re-injury of the same dermatome in adulthood. RESULTS: An increase in the number of repetitive painful stimuli, from 4 to 10 needle pricks per day, resulted in increased mechanical hypersensitivity during the neonatal period. In adulthood, repetitive painful stimuli resulted in hyposensitivity to mechanical stimuli, while thermal sensitivity was unaffected. After re-injury of the same dermatome in adulthood, the number of repetitive noxious stimuli did not affect mechanical hypersensitivity. Both needle prick groups showed an increased duration of postoperative hypersensitivity compared to control. CONCLUSION: This study shows that repetitive noxious stimulation during the early postnatal period affects acute and long-term mechanical sensitivity. Therefore, the amount of nociceptive stimuli should be minimized or adequately treated in a clinical setting.

Neonatal Plasticity of the Nociceptive System: Mechanisms, Effects, and Treatment of Repetitive Painful Procedures During NICU Admittance.

INTRODUCTION: In the Neonatal Intensive Care Unit (NICU), prematurely born infants undergo a range of skin breaking and painful procedures. At the same time, the spinal nociceptive system is in a sensitive developmental stage. Both neonatal repetitive painful procedures and their treatment can induce plasticity of the neonatal spinal nociceptive system, causing long-lasting alterations to pain processing and pain reactivity. METHODS: This review focuses on developmental processes related to the nociceptive network in the spinal dorsal horn and more specifically at mechanisms related to 1. Modulation of afferent systems; 2. The role of interneurons; 3. Descending inhibitory pathways; and 4. The central neuro-immune responses and microglial cell responses. The effects and possible mechanisms underlying the long-term effects of repetitive painful procedures on the developing nociceptive system as well as subsequent pharmacological treatment (acetaminophen, morphine) in early life are discussed. RESULTS: Repetitive stimulation of the nociceptive system in a rat model with use of needle pricks in the hind-paw closely mimics the clinical situation for infants in the NICU. CONCLUSION: Activity dependent plasticity in early postnatal life induces long-lasting alterations that then may cause altered pain perception in adulthood. For a future choice of optimal analgesic drugs these considerations have to be taken into account beyond the classical classes of drugs used nowadays.

Neonatal paracetamol treatment reduces long-term nociceptive behaviour after neonatal procedural pain in rats.

BACKGROUND: Pain from skin penetrating procedures (procedural pain) during infancy in the neonatal intensive care unit (NICU) may result in changes of nociceptive sensitivity in later life. This supports the need for pain management during such vulnerable periods in life. This study, therefore, analyses the short- and long-term consequences of neonatal paracetamol (acetaminophen) treatment on pain behaviour in an experimental rat model of neonatal procedural pain. METHODS: A repetitive needle-prick model was used, in which neonatal rats received four needle pricks into the left hind paw per day from postnatal day 0 to day 7 (P0-P7). Paracetamol (50 mg/kg/day s.c.) was administered daily (P0-P7), and sensitivity to mechanical stimuli was compared with a needle-prick/saline-treated group and to a tactile control group. At 8 weeks of age, all animals underwent an ipsilateral paw-incision, modelling postoperative pain, and the duration of hypersensitivity was assessed. RESULTS: Neonatal paracetamol administration had no effect upon short-term mechanical hypersensitivity during the first postnatal week or upon long-term baseline sensitivity from 3 to 8 weeks. However, neonatal paracetamol administration significantly reduced the postoperative mechanical hypersensitivity in young adults, caused by repetitive needle pricking. CONCLUSION: Paracetamol administration during neonatal procedural pain does not alter short-term or long-term effects on mechanical sensitivity, but does reduce the duration of increased postoperative mechanical hypersensitivity in a clinically relevant neonatal procedural pain model. WHAT DOES THIS STUDY ADD: Paracetamol can be used safely in neonatal rats. Neonatal paracetamol treatment had no effect upon short-term mechanical hypersensitivity during the first postnatal week, nor upon long-term baseline sensitivity from 3 to 8 weeks. Paracetamol treatment during the first postnatal week significantly reduced the postoperative mechanical hypersensitivity in young adult rats.

Pain prevalence and its determinants after spinal cord injury: a systematic review.

Pain prevalence studies are important as they illustrate the magnitude of pain problems in a certain patient population, such as patients living with a spinal cord injury (SCI). Strikingly, reported pain prevalence rates in SCI patients are found to vary greatly, while determinants for the differences between pain prevalence reports remain unclear. We here aim to identify determinants for the differences (heterogeneity) in pain prevalence reports through a systematic review of all SCI pain prevalence reporting studies. Literature search was done using Medline, Cumulative Index to Nursing and Allied Health Literature, ISI Web of Knowledge and Embase. Data abstraction was performed while blinded and was followed by meta-(regression)-analyses. We identified 82 studies. Study design-related determinants of SCI pain prevalence reports were pain definition strictness (mild, moderate or high), primary study goal (pain study or not), data source (retrospective or not), and in a limited number of cases response/attrition rates. While correcting for these items, population characteristics correlating with pain prevalence rates were both proportion of patients with a depression and average time after injury (positive correlations). Between-study heterogeneity may remain even after the identification/correction of above-mentioned causes of heterogeneity.Pain after SCI does seem to relate to the duration of the injury and depression, yet major causes of bias in reported pain prevalence are found to be related to the primary study goal (pain study or not), choice of pain definition and the use of retrospective data.

Sex differences in inflammatory mechanical hypersensitivity in later life of rats exposed to repetitive needle pricking as neonates.

Repetitive pain exposure of neonates in the neonatal intensive care unit (NICU) might affect proper fine-tuning of the nociceptive network, a process which continues in the postnatal period. In ex-NICU children altered basal nociception in the absence of an injury has been shown. However, the impact on nociception after an injury, e.g. surgery, is unknown. In this study we aimed to determine the effect of neonatal repetitive small painful skin-breaking procedures in both sexes on nociception in the absence and in the presence of an ongoing injury in later life. To this end the repetitive needle prick animal model was used in which neonatal Sprague­Dawley male and female rat pups received four needle pricks per day into one hind paw during the first week of life and control animals received non-painful tactile stimuli. Nociceptive thresholds to mechanical stimuli in the absence of injury, i.e. basal nociception, were not affected by neonatal repetitive needle pricking. Only male animals which received neonatal needle pricks showed increased hypersensitivity to mechanical stimuli at 24 h after ipsilateral CFA-injection. Our study shows that repetitive small needle pricks during the first week of life result in increased hypersensitivity to mechanical stimuli at 24 h after ipsilateral CFA-injection in later life in male animals and not in females.

Prevalence of pain in Parkinson's disease: a systematic review using the modified QUADAS tool.

Pain has been studied more intensely as a symptom of Parkinson's disease (PD) in recent years. However, studies on the characteristics and prevalence of pain in PD have yielded conflicting results, prompting us to do a systematic review of the literature. A systematic review of the literature was conducted, using different databases. The last inclusion date was March 15, 2011. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used, which is especially designed for judging prevalence studies on their methodological quality. Only articles that met the predefined criteria were used in this review. We found 18 articles, of which only 8 met the methodological criteria. Prevalence frequency ranges from 40% to 85% with a mean of 67.6%. Pain is most frequently located in the lower limbs, with almost one-half of all PD patients complaining about musculoskeletal pain (46.4%). The pain fluctuates with on-off periods. Surprisingly, only 52.4% of PD patients with pain used analgesics, most often nonopioids. PD patients seem to be predisposed to develop pain and physicians should be aware of pain as a common feature of PD. As many as one-half of PD patients with pain may be missing out on a potentially useful treatment, and proper treatment could increase quality of life in PD patients.

Prevalence of pain in patients with cancer: a systematic review of the past 40 years.

BACKGROUND: Despite the abundant literature on this topic, accurate prevalence estimates of pain in cancer patients are not available. We investigated the prevalence of pain in cancer patients according to the different disease stages and types of cancer. PATIENTS AND METHODS: A systematic review of the literature was conducted. An instrument especially designed for judging prevalence studies on their methodological quality was used. Methodologically acceptable articles were used in the meta-analyses. RESULTS: Fifty-two studies were used in the meta-analysis. Pooled prevalence rates of pain were calculated for four subgroups: (i) studies including patients after curative treatment, 33% [95% confidence interval (CI) 21% to 46%]; (ii) studies including patients under anticancer treatment: 59% (CI 44% to 73%); (iii) studies including patients characterised as advanced/metastatic/terminal disease, 64% (CI 58% to 69%) and (iii) studies including patients at all disease stages, 53% (CI 43% to 63%). Of the patients with pain more than one-third graded their pain as moderate or severe. Pooled prevalence of pain was >50% in all cancer types with the highest prevalence in head/neck cancer patients (70%; 95% CI 51% to 88%). CONCLUSION: Despite the clear World Health Organisation recommendations, cancer pain still is a major problem.

Percutaneous pulsed radiofrequency treatment of the cervical dorsal root ganglion in the treatment of chronic cervical pain syndromes: a clinical audit.

Cervicogenic headache and cervicobrachialgia are frequent diagnoses of chronic cervical pain. After failure of conservative treatment, an interventional approach may be indicated in the absence of any indication for causal surgical treatment. The pulsed radiofrequency (PRF) technique exposes the nerve to a high-frequency electric field while the temperature of the electrode tip does not exceed 42°C. This method is thought to be nondestructive and almost free of neurologic side effects and complications. Our extended pilot study was performed to confirm the perceived efficacy of PRF for short- and long-term relief of chronic cervical pain. We carried out a clinical audit of the first 18 patients treated with PRF at the cervical dorsal root ganglion. An independent evaluator reviewed the medical records. Patients with good clinical results at 8 weeks were evaluated for long-term effect (> 6 months), based on a 7-point Likert scale. Thirteen patients (72%) showed short-term clinical success (≥ 50% pain relief). Mean follow-up was 19.4 months (SD 8.9 months), maximum 2.5 years. The duration of satisfactory pain relief (6 or 7 on the Likert scale) varied between 2 and over 30 months, with a mean duration of 9.2 months (SD 11.2 months). Kaplan-Meier analysis illustrated that 50% of patients experienced success 3 months after treatment. We could not identify predictive variables for clinical outcome. None of the patients reported post-treatment neuritis or other adverse events. To our knowledge, this is the first documented series of chronic cervical pain syndromes treated with PRF. Satisfactory pain relief of at least 50% was achieved in 13 of 18 (72%) patients at 8 weeks. More than one year after treatment, six patients (33%) continue to rate treatment outcome as good or very good. No side effects were reported. j.

MR imaging of alar ligament in whiplash-associated disorders: an observer study.

Rotational CT studies have been previously used in whiplash-associated disorders (WAD) to document rotatory instability of the upper cervical spine thought to be due to alar ligamentous injury. More recently MR imaging has been employed to image such injury more directly. Our study aimed to assess the reliability and reproducibility of such MRI findings. In 12 WAD patients and six asymptomatic controls the alar ligaments were imaged in the coronal plane with an 0.5-T MRI system using a quadrature neck coil and applying a fast spin echo proton density/T2-weighted sequence (TR/TE/ETL 2,500/18 ms/16, FOV 140 mm, matrix 200 x 256, 16 x 3 mm slices, scan time 25 min). Images were graded for symmetry of imaging plane using a 3-point scale and also for presence of ligamentous injury with a 4-point scale, by two independent observers on two separate occasions. The alar ligaments could be identified in all cases. Asymmetry of the imaging plane was found to some degree in over half of the cases. Such images were much more likely to be graded as indicating injury. Of a total of 72 assessments, clearly and probably normal grades were given in 75%, and clearly or probably abnormal grades in 25%. Kappa values for intra- and inter-observer agreement were moderate to very poor, however, and the grading system could not reliably distinguish between patients and controls. It was concluded that with MRI techniques presently employed, alar ligamentous damage as a causative factor in WAD has not been proven.

CT study of craniovertebral rotation in whiplash injury.

The present study investigates the diagnostic value of rotatory computed tomography (CT) examinations in normal subjects and patients with whiplash associated disorders (WAD), with the aim of reproducing earlier findings of rotatory CT studies. Forty-seven WAD patients with persistent complaints after a rear-end collision (non-cranial contact acceleration/deceleration trauma) were enrolled in this study. To guarantee a maximally homogeneous study population, only WAD patients with a marked passive cervical retroflexion restriction were included. Transversal CT slices in left and right rotation were made for all cervical levels (the skull included). CT slices in neutral position were used to reconstruct partially depicted vertebrae. Absolute rotatory values were estimated according the method of Penning and Dvorak. For all levels the relative rotatory (RR) value was calculated by dividing absolute rotation values of a particular cervical level by the corresponding total cervical rotation. The measuring error was estimated by comparing the findings of two separately performed measuring procedures. Two age groups of WAD patients were formed. A younger group was matched for age with 26 normal healthy volunteers (the original data of an earlier study). The use of neutral CT slices for reconstruction of a partially depicted cervical vertebra resulted in a measurement error of 1.9 degrees at the level of C0/C1 (occiput/atlas) and 3.5 degrees at C1/C2. Suspected hypermobility as defined by Dvorak was rare in our WAD patients (6.4% C0/C1 and 10.6% C1/C2). RR values at C0/C1 were significantly larger in 79% of the WAD patients. Discriminant analysis of the RR values showed 80% correctly classified WAD patients. Only 11.5% of the normal subjects were classified as false-positive. Since no hypermobility was found at C1/C2, a traumatic lesion of the alar ligaments is less likely. It was concluded that the use of absolute rotation values in rotatory CT scan procedures has a low diagnostic value in WAD patients. Excessive RR values were only found at C0/C1. A traumatic lesion of the ligaments at C0/C1, which prevent vertical translation of the skull with regard to the atlas, is hypothesised. The results of the discriminant analysis of the RR values make this method applicable for the individual WAD patient in daily practice.

Sitting and low back pain: the positive effect of rotary dynamic stimuli during prolonged sitting.

In this study the effect of dynamic stimuli on low back pain during prolonged sitting was investigated. The pain experience of two groups of 60 subjects with a specific low back pain was recorded. All subjects were investigated on pain behaviour by the Multidimensional Pain Inventory (MPI) and pain was measured on an open visual analogue scale (VAS). During sitting, one group received dynamic stimuli that were generated by alternating rotations in the horizontal plane of the seat of the chair, with back and arm rests in fixed position. Two different frequencies of rotation were applied in subgroups. The authors concluded that such stimuli, especially of the lower frequency, reduced pain in prolonged sitting.