Pinprick Stimulation Research Articles

Signs of hyperpathia in chronic peripheral neuropathic pain.

Neuropathic pain is pain due to a disease or lesion of the somatosensory system, and can be either spontaneous, evoked or both. Hyperpathia is a type of evoked pain defined by IASP as 'a painful syndrome characterized by an abnormally painful reaction to a stimulus, especially a repetitive stimulus, as well as an increased threshold'. The literature is sparse, and definitions are unclear and inconsistent. The aim of this study was to examine for the presence of mechanical hyperpathia in a heterogeneous group of patients with peripheral neuropathic pain and correlate signs of hyperpathia with other sensory signs. Patients were examined with graded pinprick stimuli to obtain a stimulus-response curve and repetitive pinprick stimuli to assess increase in pain over time and aftersensations. Then, patients were grouped based on the likelihood of having mechanical hyperpathia with either a steep stimulus-response curve or a steep curve on the repetitive pinprick test and results were correlated to mechanical detection and pain thresholds and other outcomes from a full quantitative sensory testing. We included 124 patients with documented peripheral neuropathic pain. Patients with a steep stimulus-response curve did not overlap with patients with a steep curve on the repetitive pinprick test and both groups more often had decreased rather than increased detection and pain thresholds. Our study questions the concept of hyperpathia and suggests that more studies are needed to identify which symptoms and signs group together and might form a syndrome. Hyperpathia is a syndrome of evoked pain. It is poorly defined and little is known about its clinical presentation. Since it is part of pain symptomatology it is important to have a clear definition and understand the pathophysiology behind. This study explored signs of hyperpathia in a heterogeneous group of patients with peripheral neuropathic pain. We used stimulus-response function and repetitive pinprick stimulation to group patients based on the IASP definition. More studies are needed to understand how symptoms and signs coincide.

A Preterm Rat Model for Pain Studies.

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain sensitivity. The primary objective of this protocol was to investigate the impact of neonatal pinprick stimuli on the pain threshold in the later stages of life using a preterm rat model. By establishing this model, we aim to advance the research on understanding and managing early postnatal pain associated with prematurity. The findings of this study indicate that while the baseline thresholds to mechanical stimuli remained unaffected, there was a notable increase in mechanical hypersensitivity following complete Freund's adjuvant (CFA) injection in adult rats. Interestingly, compared with male rats, female rats demonstrated heightened inflammatory hypersensitivity. Notably, maternal behavior, the weight of the litters, and the growth trajectory of the offspring remained unchanged by the stimulation. The manifestation of altered nociceptive responses in adulthood after neonatal painful stimuli could be indicative of changes in sensory processing and the functioning of glucocorticoid receptors. However, further research is needed to understand the underlying mechanisms involved and to develop interventions for the consequences of prematurity and neonatal pain in adults.

A back-translational study of descending interactions with the induction of hyperalgesia by high-frequency electrical stimulation in rats and humans.

In humans and animals, high-frequency electrocutaneous stimulation (HFS) induces an "early long-term potentiation-like" sensitisation, where synaptic plasticity is underpinned by an ill-defined interaction between peripheral input and central modulatory processes. The relative contributions of these processes to the initial pain or nociceptive response likely differ from those that underpin development of the heightened response. To investigate the impact of HFS-induced hyperalgesia on pain and nociception in perception and neural terms, respectively, and to explore the impact of descending inhibitory pathway activation on the development of HFS-induced hyperalgesia, we performed parallel studies utilising identical stimuli to apply HFS concurrent to (1) a conditioned pain modulation paradigm during psychophysical testing in healthy humans or (2) a diffuse noxious inhibitory controls paradigm during in vivo electrophysiological recording of spinal neurones in healthy anaesthetised rats. High-frequency electrocutaneous stimulation alone induced enhanced perceptual responses to pinprick stimuli in cutaneous areas secondary to the area of electrical stimulation in humans and increased the excitability of spinal neurones which exhibited stimulus intensity-dependent coded responses to pinprick stimulation in a manner that tracked with human psychophysics, supporting their translational validity. Application of a distant noxious conditioning stimulus during HFS did not alter perceived primary or secondary hyperalgesia in humans or the development of primary or secondary neuronal hyperexcitability in rats compared with HFS alone, suggesting that, upon HFS-response initiation in a healthy nervous system, excitatory signalling escapes inhibitory control. Therefore, in this model, dampening facilitatory mechanisms rather than augmenting top-down inhibitions could prevent pain development.

Effects of repetitive pinprick stimulation on preterm offspring: Alterations in nociceptive responses and inflammatory hypersensitivity in adulthood

IntroductionThis study investigates the effects of repetitive pinprick stimulation on preterm offspring and its impact on nociceptive responses and inflammatory hypersensitivity in adulthood. ObjectivesThe objective is to shed light on the potential long-term consequences of neonatal pain and prematurity on sensory processing. MethodsTerm and preterm rats were subjected to repetitive pinprick (PP) stimulation or control (CC) during the neonatal period. Adult rats received CFA injection to induce inflammatory hypersensitivity, and mechanical hypersensitivity was measured. Gender differences in inflammatory hypersensitivity were also examined. Maternal behavior, litter weight, and offspring growth were monitored to assess any potential influences of the stimulation on these parameters. ResultsIn preterm rats, the PP stimulation did not affect baseline thresholds to mechanical stimuli, but increased mechanical hypersensitivity after CFA injection in adult rats. Females exhibited greater inflammatory hypersensitivity compared to males. Maternal behavior, litter weight, and offspring growth were not influenced by the stimulation. PP stimulation during the neonatal period led to changes in nociceptive responses in adulthood, potentially altering sensory processing. ConclusionPP stimulation in preterm rats during the neonatal period resulted in changes in nociceptive responses in adulthood, leading to increased inflammatory hypersensitivity. The study emphasizes how early development can significantly impact sensory processing and further highlights the potential long-term consequences of prematurity and neonatal pain on this processing.

Pinprick-induced gamma-band oscillations are not a useful electrophysiological marker of pinprick hypersensitivity in humans

ObjectiveThis study aimed to investigate scalp gamma-band oscillations (GBOs) induced by mechanical stimuli activating skin nociceptors before and after the induction of mechanical hypersensitivity using high-frequency electrical stimulation (HFS) of the skin. MethodsIn twenty healthy volunteers, we recorded the electroencephalogram during robot-controlled mechanical pinprick stimulation (512 mN) applied at the right ventral forearm before and after HFS. ResultsHFS induced a significant increase in mechanical pinprick sensitivity, but this increased pinprick sensitivity was, at the group level, not accompanied by a significant increase in GBOs. Visual inspection of the individual data revealed that possible GBOs were present in eight out of twenty participants (40%) and the frequency of these GBOs varied substantially across participants. ConclusionsBased on the low number of participants showing GBOs we question the (clinical) utility of mechanically-induced GBOs as an electrophysiological marker of pinprick hypersensitivity in humans. SignificanceMechanical pinprick-induced scalp GBOs are not useful for evaluating mechanical pinprick hypersensitivity in humans.

Thoracic pain in patients with chronic interstitial lung disease-an underestimated symptom.

Prevalence and predisposing factors for the development of thoracic pain (TP) in patients with chronic interstitial lung disease (cILD) are largely unknown. Underestimation and insufficient therapy of pain can lead to worsened ventilatory function. Quantitative sensory testing is an established tool for characterization of chronic pain and its neuropathic components. We investigated frequency and intensity of TP in cILD patients and the potential association with lung function and quality of life. We prospectively investigated patients with chronic interstitial lung disease to analyze risk factors for the development of thoracic pain and quantify thoracic pain through quantitative sensory testing. In addition, we studied the relationship between pain sensitivity and lung function impairment. Seventy-eight patients with chronic interstitial lung disease and 36 healthy controls (HCs) were included. Thoracic pain occurred in 38 of 78 patients (49%), most frequently in 13 of 18 (72%, p = 0.02) patients with pulmonary sarcoidosis. The occurrence was mostly spontaneous and not related to thoracic surgical interventions (76%, p = 0.48). Patients with thoracic pain showed a significant impairment of mental well-being (p = 0.004). A higher sensitivity to pinprick stimulation during QST can be observed in patients with thoracic pain (p < 0.001). Steroid treatment was associated with lower sensitivity within thermal (p = 0.034 and p = 0.032) and pressure pain testing (p = 0.046). We observed a significant correlation between total lung capacity and thermal (p = 0.019 and p = 0.03) or pressure pain sensitivity (p = 0.006 and p = 0.024). This study was performed to investigate prevalence, risk factors and thoracic pain in patients with chronic interstitial lung disease. Thoracic pain mostly occurs spontaneous as a frequent symptom, and seems to be an underestimated symptom in patients with chronic interstitial lung disease, especially those with pulmonary sarcoidosis. Timely identification of thoracic pain may allow starting symptomatic treatment at early stage, before impairment in quality of life occurs. https://www.drks.de/drks_web/, Deutsches Register Klinischer Studien (DRKS) DRKS00022978.

Pain-autonomic measures reveal nociceptive sensitization in complex regional pain syndrome.

Allodynia and hyperalgesia are common signs in individuals with complex regional pain syndrome (CRPS), mainly attributed to sensitization of the nociceptive system. Appropriate diagnostic tools for the objective assessment of such hypersensitivities are still lacking, which are essential for the development of mechanism-based treatment strategies. This study investigated the use of pain-autonomic readouts to objectively detect sensitization processes in CRPS. Twenty individuals with chronic CRPS were recruited for the study alongside 16 age- and sex-matched healthy controls (HC). All individuals underwent quantitative sensory testing and neurophysiological assessments. Sympathetic skin responses (SSRs) were recorded in response to 15 pinprick and 15 noxious heat stimuli of the affected (CRPS hand/foot) and a control area (contralateral shoulder/hand). Individuals with CRPS showed increased mechanical pain sensitivity and increased SSR amplitudes compared with HC in response to pinprick and heat stimulation of the affected (p< 0.001), but not in the control area (p> 0.05). Habituation of pinprick-induced SSRs was reduced in CRPS compared to HC in both the affected (p= 0.018) and slightly in the control area (p= 0.048). Habituation of heat-induced SSR was reduced in CRPS in the affected (p= 0.008), but not the control area (p= 0.053). This is the first study demonstrating clinical evidence that pain-related autonomic responses may represent objective tools to quantify sensitization processes along the nociceptive neuraxis in CRPS (e.g. widespread hyperexcitability). Pain-autonomic readouts could help scrutinize mechanisms underlying the development and maintenance of chronic pain in CRPS and provide valuable metrics to detect mechanism-based treatment responses in clinical trials. This study provides clinical evidence that autonomic measures to noxious stimuli can objectively detect sensitization processes along the nociceptive neuraxis in complex regional pain syndrome (CRPS) (e.g. widespread hyperexcitability). Pain-autonomic readouts may represent valuable tools to explore pathophysiological mechanisms in a variety of pain patients and offer novel avenues to help guide mechanism-based therapeutic strategies.

Reliability of Upper Limb Pin-Prick Stimulation With Electroencephalography: Evoked Potentials, Spectra and Source Localization.

In order for electroencephalography (EEG) with sensory stimuli measures to be used in research and neurological clinical practice, demonstration of reliability is needed. However, this is rarely examined. Here we studied the test-retest reliability of the EEG latency and amplitude of evoked potentials and spectra as well as identifying the sources during pin-prick stimulation. We recorded EEG in 23 healthy older adults who underwent a protocol of pin-prick stimulation on the dominant and non-dominant hand. EEG was recorded in a second session with rest intervals of 1 week. For EEG electrodes Fz, Cz, and Pz peak amplitude, latency and frequency spectra for pin-prick evoked potentials was determined and test-retest reliability was assessed. Substantial reliability ICC scores (0.76–0.79) were identified for evoked potential negative-positive amplitude from the left hand at C4 channel and positive peak latency when stimulating the right hand at Cz channel. Frequency spectra showed consistent increase of low-frequency band activity (< 5 Hz) and also in theta and alpha bands in first 0.25 s. Almost perfect reliability scores were found for activity at both low-frequency and theta bands (ICC scores: 0.81–0.98). Sources were identified in the primary somatosensory and motor cortices in relation to the positive peak using s-LORETA analysis. Measuring the frequency response from the pin-prick evoked potentials may allow the reliable assessment of central somatosensory impairment in the clinical setting.

Priming of central and peripheral mechanisms with heat and cutaneous capsaicin facilitates secondary hyperalgesia to high-frequency electrical stimulation

Heat/capsaicin sensitization and electrical high-frequency stimulation (HFS) are well-known models of secondary hyperalgesia, a phenomenon related to chronic pain conditions. This study investigated whether priming with heat/capsaicin would facilitate hyperalgesia to HFS in healthy subjects. Heat/capsaicin priming consisted of a 45°C heat stimulation for 5 min followed by a topical capsaicin patch (4 × 4 cm) for 30 min on the volar forearm of 20 subjects. HFS (100 Hz, 5 times 1 s, minimum 1.5 mA) was subsequently delivered through a transcutaneous pin electrode approximately 1.5 cm proximal to the heat/capsaicin application. Two sessions were applied in a crossover design; traditional HFS (HFS) and heat/capsaicin sensitization followed by HFS (HFS + HEAT/CAPS). Heat pain threshold (HPT), mechanical pain sensitivity (MPS), and superficial blood perfusion were assessed at baseline, after capsaicin removal, and up to 40 min after HFS. MPS was assessed with pin-prick stimulation (128 mN and 256 mN) in the area adjacent to both HFS and heat/capsaicin, distal but adjacent to heat/capsaicin and in a distal control area. HPT was assessed in the area of heat/capsaicin. Higher sensitivity to 128 mN pin-prick stimulation (difference from baseline and control area) was observed in the HFS + HEAT/CAPS session than in the HFS session 20 and 30 min after HFS. Furthermore, sensitivity was increased after HFS + HEAT/CAPS compared with after heat/capsaicin in the area adjacent to both paradigms, but not in the area distal to heat/capsaicin. Results indicate that heat/capsaicin causes priming of the central and peripheral nervous system, which facilitates secondary mechanical hyperalgesia to HFS.NEW & NOTEWORTHY High-frequency electrical stimulation (HFS) and heat/capsaicin sensitization are well-known models of secondary hyperalgesia. The results from the current study indicate that increased sensitivity to 128 mN pin-prick stimulation can be obtained when HFS is delivered following an already established heightened central hyperexcitability provoked by heat/capsaicin sensitization.

Tenderness of the Skin after Chemical Stimulation of Underlying Temporal and Thoracolumbar Fasciae Reveals Somatosensory Crosstalk between Superficial and Deep Tissues.

Musculoskeletal pain is often associated with pain referred to adjacent areas or skin. So far, no study has analyzed the somatosensory changes of the skin after the stimulation of different underlying fasciae. The current study aimed to investigate heterotopic somatosensory crosstalk between deep tissue (muscle or fascia) and superficial tissue (skin) using two established models of deep tissue pain (namely focal high frequency electrical stimulation (HFS) (100 pulses of constant current electrical stimulation at 10× detection threshold) or the injection of hypertonic saline in stimulus locations as verified using ultrasound). In a methodological pilot experiment in the TLF, different injection volumes of hypertonic saline (50–800 µL) revealed that small injection volumes were most suitable, as they elicited sufficient pain but avoided the complication of the numbing pinprick sensitivity encountered after the injection of a very large volume (800 µL), particularly following muscle injections. The testing of fascia at different body sites revealed that 100 µL of hypertonic saline in the temporal fascia and TLF elicited significant pinprick hyperalgesia in the overlying skin (–26.2% and –23.5% adjusted threshold reduction, p < 0.001 and p < 0.05, respectively), but not the trapezius fascia or iliotibial band. Notably, both estimates of hyperalgesia were significantly correlated (r = 0.61, p < 0.005). Comprehensive somatosensory testing (DFNS standard) revealed that no test parameter was changed significantly following electrical HFS. The experiments demonstrated that fascia stimulation at a sufficient stimulus intensity elicited significant across-tissue facilitation to pinprick stimulation (referred hyperalgesia), a hallmark sign of nociceptive central sensitization.

Central sensitization of nociceptive pathways demonstrated by robot-controlled pinprick-evoked brain potentials

ObjectiveThe aim of this study was to assess the effect of central sensitization, induced by high frequency electrical stimulation of the skin (HFS), on pinprick-evoked brain potentials (PEPs) using robot-controlled mechanical pinprick stimulation and a stimulus evaluation task. MethodsIn 16 healthy volunteers HFS was applied to the right volar forearm. Robot- controlled pinprick stimuli (64 mN) were applied before and 20 minutes after HFS to the skin surrounding the area onto which HFS was applied. During pinprick stimulation, the EEG was recorded and the quality of perception and perceived intensity of the pinprick stimuli was collected. ResultsAfter HFS, the skin surrounding the site at which HFS was delivered showed increased mechanical pinprick sensitivity. Both the early-latency negative peak of PEPs and the later-latency peak were significantly increased after HFS. ConclusionsThis study shows increased PEPs after HFS when they are elicited by a robot-controlled mechanical pinprick stimulator and participants are engaged in a stimulus evaluation task during pinprick stimulation. SignificanceThis is the first study that shows a significant increase of both PEP peaks, and therefore, it provides a preferred setup for assessing the function of mechanical nociceptive pathways in the context of central sensitization.

Assessment of Somatosensory and Psychosocial Function of Patients With Trigeminal Nerve Damage.

The present study assessed somatosensory changes related to trigeminal nerve damage using extensive evaluation tools and assessed the effect of such damage on the patients' psychosocial status and quality of life compared with healthy participants. In 37 patients with intraorally or extraorally presenting trigeminal nerve damage diagnosed as painful or nonpainful posttraumatic trigeminal neuropathy, psychophysical tests like quantitative sensory testing (QST) and qualitative sensory testing and the electrophysiological "nociceptive-specific" blink reflex were performed. The patients and 20 healthy participants completed a set of questionnaires assessing their psychosocial status and quality of life. A loss or gain of somatosensory function was seen in at least 1 QST parameter in >88.9% of the patients. Patients in whom extraoral QST was performed showed an overall loss of somatosensory function, whereas intraoral QST showed a general gain of somatosensory function. Qualitative sensory testing identified a side-to-side difference in the tactile and pinprick stimulation in >77% of the patients. An abnormal "nociceptive-specific" blink reflex response was seen in 42.1% to 71.4% of patients dependent on the trigeminal branch stimulated, though comparisons with healthy reference values showed ambiguous results. Compared with the healthy participants, patients showed higher scores for pain catastrophizing, symptoms of depression and anxiety, limited jaw function, more somatic symptoms, and significantly impaired oral health-related quality of life (all P<0.038). The results from the present study showed presence of varied somatosensory abnormalities when assessed using psychophysical and electrophysiological investigations and a significantly impaired psychosocial status.

Anal reflex versus bulbocavernosus reflex in evaluation of patients with spinal cord injury.

The examination of sacral reflexes provides an important method to differentiate an upper motor neuron vs lower motor neuron spinal cord injury (SCI). Two common sacral mediated reflexes used as part of the neurological assessment include the bulbocavernosus reflex (BCR) and anal reflex. As the clinical information from these tests are similar, we suggest that the anal reflex provides a better first option as a non-invasive clinical assessment of sacral reflex status in clinical practice in SCI as the testing for the anal reflex is less intrusive and already being performed as part of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) by pinprick stimulation of the S4-5 dermatome.

An fMRI study on runner’s high and exercise-induced hypoalgesia after a 2-h-run in trained non-elite male athletes

While elite long-distance runners experience hypoalgesia and sometimes runner’s high after running, these phenomena are rarely explored in non-elite runners. Therefore, we examined the effect of a 2-h-run on mood and pain processing in 15 non-elite male runners using repeated painful and nonpainful pinprick stimulation and functional magnetic resonance imaging (fMRI). Pain ratings, pressure pain stimulus responses, and euphoria ratings were assessed immediately after a 2-h-run and at a run-free control day (RFC). Analysis of a half-standardized-interview indicates an improvement of mood. However, there was no elevation of euphoria. Neither in pain ratings nor in fMRI data, we observed less pain perception after the 2-h-run. However, endurance training increases the blood flow of the hippocampal formation. Furthermore, more pressure was required to evoke a clear pain sensation in highly trained athletes at post-run vs. RFC. In summary, we found behavioral and neuroimaging signs that underpin the positive effects of endurance exercise. However, the results also suggest that hypoalgesia and “runner’s high” experience are rather rare phenomena in non-elite endurance runners.

Pinprick Evoked Potentials-Reliable Acquisition in Healthy Human Volunteers.

Pinprick evoked potentials (PEPs) represent a novel tool to assess the functional integrity of mechano-nociceptive pathways with a potential toward objectifying sensory deficits and gain seen in neurological disorders. The aim of the present study was to evaluate the feasibility and reliability of PEPs with respect to age, stimulation site, and skin type. Electroencephalographic responses evoked by two pinprick stimulation intensities (128 mN and 256 mN) applied at three sites (hand dorsum, palmar digit II, and foot dorsum) were recorded in 30 healthy individuals. Test-retest reliability was performed for the vertex negative-positive complex amplitudes, N-latencies, and pain ratings evoked by the 256mN stimulation intensity. Feasibility of PEP acquisition was demonstrated across age groups, with higher proportions of evoked potentials (>85%) for the 256mN stimulation intensity. Reliability analyses, that is, Bland-Altman and intraclass correlation coefficients, revealed poor to excellent reliability upon retest depending on the stimulation sites. This study highlights the reliability of PEP acquisition from cervical and lumbar segments across clinically representative age groups. Future methodological improvements might further strengthen PEP reliability in order to complement clinical neurophysiology of sensory nerve fibers by a more specific assessment of mechano-nociceptive pathways. Beyond looking at sensory deficits, PEPs may also become applicable to revealing signs of central sensitization, complementing the clinical assessment of mechanical hyperalgesia.

Central sensitization increases the pupil dilation elicited by mechanical pinprick stimulation.

High-frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization (CS), manifested as increased pinprick sensitivity of the skin surrounding the site of HFS. Our aim was to assess the effect of CS on pinprick-evoked pupil dilation responses (PDRs) and pinprick-evoked brain potentials (PEPs). We hypothesized that the increase in the positive wave of PEPs following HFS would result from an enhanced pinprick-evoked phasic response of the locus coeruleus-noradrenergic system (LC-NS), indicated by enhanced PDRs. In 14 healthy volunteers, 64- and 96-mN pinprick stimuli were delivered to the left and right forearms, before and 20 minutes after HFS was applied to one of the two forearms. Both PEPs and pinprick-evoked PDRs were recorded. After HFS, pinprick stimuli were perceived as more intense at the HFS-treated arm compared with baseline and control site, and this increase was similar for both stimulation intensities. Importantly, the pinprick-evoked PDR was also increased, and the increase was stronger for 64- compared with 96-mN stimulation. This is in line with our previous results showing a stronger increase of the PEP positivity at 64 vs. 96-mN stimulation and suggests that the increase in PEP positivity observed in previous studies could relate, at least in part, to enhanced LC-NS activity. However, there was no increase of the PEP positivity in the present study, indicating that enhanced LC-NS activity is not the only determinant of the HFS-induced enhancement of PEPs. Altogether, our results indicate that PDRs are more sensitive for detecting CS than PEPs. NEW & NOTEWORTHY We provide the first demonstration in humans that activity-dependent central sensitization increases pinprick-evoked autonomic arousal measured by enhanced pupil dilation response.

Repeated neonatal needle-prick stimulation increases inflammatory mechanical hypersensitivity in adult rats

Background and aimsNewborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period. MethodsThe animals were submitted to repetitive needle pricking from the second to the fifteenth postnatal day (PND 2–15). Maternal behavior and litter weight were evaluated during this period. Mechanical sensitivity to pain was assessed in offsprings during the adulthood by exposing them to inflammatory stimuli, including formalin test or the Freund’s complete adjuvant (CFA) injection followed by the electronic von Frey test at 0, 3, 6 and 24 h later. ResultsMaternal behavior and litter weight were not altered by pinprick stimuli during PND 2–15. Additionally, pinprick stimulation reduced the paw withdrawal threshold in CFA-injected animals compared to control. In the formalin test, there was a difference between the genders. Female rats are statically more sensitive to formalin stimulation and showed an increased licking time in both the first and second phases and increased number of flinches in second phase. ConclusionsExperiencing early life repetitive pain exposure increased inflammatory pain sensitivity in adult offspring rats and female rats are more sensitive to chemical stimulation. ImplicationsFuture investigations of the mechanisms involved in this effect may contribute to the improvement of the understanding of inflammatory pain sensitivity differences.

Pain assessment in hospitalized spinal cord injured patients - a controlled cross-sectional study.

Background and aims Following spinal cord injury (SCI), a majority of individuals may develop neuropathic pain, which further reduces quality of life. Pain is difficult to treat by medication; in fact, medication overuse may aggravate neuropathic pain in SCI by causing central sensitization (CS): a mechanism of hyper-reactivity of the dorsal horn neurons in the spinal cord with amplified cerebral pain response. The purpose of this study was to examine the presence of neuropathic pain and CS above the spinal lesion in SCI, and to investigate whether injury characteristics or medication influenced pain response. Methods Twenty-four SCI patients with various injury characteristics (eight subacute, traumatic injuries, eight chronic, traumatic injuries, eight non-traumatic injuries) and 12 able-bodied controls underwent sensory testing:pressure algometry, Von Frey filaments (sensitivity), and repetitive pinprick stimulation (pain windup). SCI participants also fulfilled a modified version of the McGill Pain Questionnaire. Data were analyzed regarding (i) SCI patients compared with controlgroup and (ii) SCI subgroup comparison (grouped by a) injury characteristics and (b) intake of analgesics, where low-medicated subgroup were prescribed only non-opioids and high-medicated potent opioids). Results Neuropathic pain was present in 21 of 24 SCI patients. Chronic and non-traumatic SCI patients reported considerably higher present pain intensity than sub-acute traumatic SCI patients on a five-point scale (3.13±0.99, 1.75±1.75 and 0.13±0.35, respectively, p<0.005). Reduced pressure pain detection thresholds (PPDT) were found in SCI patients at several supra-lesional anatomical points compared to controls. Contrarily, tactile detection thresholds were higher in SCI. SCI subgroup analyses showed that i) the low-medicated SCI subgroup displayed significantly lower PPDT compared to the high-medicated subgroup, ii) pain-windup was present in all subgroups although the sub-acute and non-traumatic subgroups displayed lesser pain windup than controls, and the chronic SCI subgroup mainly displayed higher pain windup. Conclusions The reduced PPDT found above lesion suggests the presence of CS in SCI. However, findings regarding SCI subgroup comparison did not support our hypothesis that more medication leads to increased CS. Implications The development of CS may complicate diagnosis and pain treatment following SCI. Prospective studies of SCI with a healthy control group are needed.

High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of increased mechanical pinprick sensitivity.

High frequency electrical stimulation (HFS) of the skin induces increased pinprick sensitivity in the surrounding unconditioned skin. The aim of the present study was to investigate the contribution of A-fiber nociceptors to this increased pinprick sensitivity. For this we assessed if the perception and brain responses elicited by low-intensity intra-epidermal electrical stimulation (IES), a method preferentially activating Aδ-fiber nociceptors, are increased in the area of HFS-induced increased pinprick sensitivity. HFS was delivered to one of the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1) and 45 minutes after HFS (T2). In all participants, HFS induced an increase in pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This increase was significant at both T1 and T2. HFS did not affect the percept elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain potentials, both at T1 and at T2. Our results show that HFS induces a long-lasting enhancement of the N2 wave elicited by IES in the area of secondary hyperalgesia, indicating that HFS enhances the responsiveness of the central nervous system to nociceptive A-fiber input. However, we found no evidence that HFS affects the perception elicited by IES, which may suggest that the population of nociceptors that mediate the perception elicited by IES do not contribute to HFS-induced increased pinprick sensitivity.

Expectation of exercise in trained athletes results in a reduction of central processing to nociceptive stimulation

A single endurance exercise session was shown to lead to a reduction of pain perception and an elevation of mood. We hypothesized that athletes, who regularly practice endurance, might also induce changes in mood and pain processing in expectation of an endurance session. We compared the expectation effects of a 2-h-run on mood and pain processing to a run-free control day (RFC). Fifteen trained runners were assessed with repeated painful and nonpainful pinprick stimulation in a functional magnetic resonance imaging (fMRI) scanner prior to a 2-h-run and at RFC. Pain ratings, pressure pain stimulus-response functions, and euphoria ratings were also assessed. There were no mean expectation effects on any of the behavioral measures. However, highly trained athletes needed more pressure to evoke a pain rating of 46 pre-run vs. RFC but were less euphoric pre-run vs. RFC. Furthermore, analysis of brain activities to painful stimuli applied immediately before the 2-h-run compared to RFC revealed increased activation in the medial prefrontal cortex (mPFC) and reduced activation in posterior insula. Additionally, less trained athletes had reduced activation in posterior insula to painful stimulation pre-run vs. RFC compared to highly trained athletes. The results suggest reduced central pain processing in expectation of an endurance run and an association between the amount of the expectation effect and training frequency which differs depending on the stimuli applied.