The latest medical research on Pain Medicine

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about pain medicine gathered by our medical AI research bot.

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Burst Occipital Nerve Stimulation for Chronic Migraine and Chronic Cluster Headache.


Occipital nerve stimulation (ONS) is widely used for headache syndromes including chronic migraine (CM) and chronic cluster headache (CCH). The paraesthesia associated with tonic stimulation can be bothersome and can limit therapy. It is now clear in spinal cord stimulation that paraesthesia-free waveforms can produce effective analgesia, but this has not been reported in ONS for CM or CCH.

Seventeen patients (12 CM and 5 CCH) were treated with bilateral burst pattern ONS, including 4 who had previously had tonic ONS. Results were assessed in terms of the frequency of headaches (number of headache days per month for CM, and number of attacks per day for CCH) and their intensity on the numeric pain rating scale.

Burst ONS produced a statistically significant mean reduction of 10.2 headache days per month in CM. In CCH, there were significant mean reductions in headache frequency (92%) and intensity (42%).

Paraesthesia is not necessary for good quality analgesia in ONS. Larger studies will be required to determine whether the efficacies of the two stimulation modes differ. Burst ONS is imperceptible and therefore potentially amenable to robustly blinded clinical trials.

Observations of Autonomic Variability Following Central Neuromodulation for Chronic Neuropathic Pain in Spinal Cord Injury.


Spinal cord injury (SCI) persons with chronic neuropathic pain (NP) demonstrate maladaptive autonomic profiles compared to SCI counterparts without NP (SCI - NP) or able-bodied (AB) controls. These aberrations may be secondary to maladaptive neuroplasticity in the shared circuitry of the pain neuromatrix-central autonomic network interface (PNM-CAN). In this study, we explored the proposed PNM-CAN mechanism in SCI + NP and AB cohorts following centrally-directed neuromodulation to assess if the PNM and CAN are capable of being differentially modulated.

Central neuromodulation was administered via breathing-controlled electrical stimulation (BreEStim), previously evidenced to operate at the PNM. To quantify CAN activity, conventional heart rate variability (HRV) recordings were used to gather time and frequency domain parameters of autonomic modulation. SCI + NP (n = 10) and AB (n = 13) cohorts received null and active BreEStim randomly in crossover fashion. HRV data were gathered pretest and 30 minutes posttest. Pain modulation was quantified at both time-points by visual analog scale (VAS) for SCI + NP persons and electrical detection and pain threshold levels (EDT, EPT) for AB persons.

Following active BreEStim only, SCI + NP persons demonstrated increased parasympathetic tone (increased NN50, p = 0.03, and pNN50, p = 0.02, HRV parameters). This parasympathetic restoration was associated with analgesia (VAS reduction, p < 0.01). Similarly, AB persons demonstrated increased noxious tolerance (increased EPT, p = 0.03, with preserved EDL, p = 0.78) only following active BreEStim. However, this increased pain threshold was not associated with autonomic changes.

Central modulation targeting the PNM produced autonomic changes in SCI + NP persons but not AB persons. These findings suggest that AB persons exhibit intact CAN mechanisms capable of compensating for PNM aberrations or simply that SCI + NP persons exhibit altered PNM-CAN machinery altogether. Our collective findings confirm the interconnectedness and maladaptive plasticity of PNM-CAN machinery in SCI + NP persons and suggest that the PNM and CAN circuitry can be differentially modulated.

Age Related Differences in the Acute Pain Facial Expression During Infancy.

Eur J Pain

Oster's (2005) ontogenetic perspective on the development of emotional expressions in infants holds that infants' facial and vocal expressions evolved to serve crucial communicative functions in infancy and contribute to infants' survival. Infants' facial expressions should be contextualized by their own developmental stage rather than presuppositions from verbal populations. The overall aim of this paper was to examine age differences in the temporal patterning of elucidated facial expressions in the first minute following vaccination injections.

One hundred infants were videotaped longitudinally (2-, 4-, 6-, and 12- months) during their routine vaccination appointment over the first year of life and 5 major negative facial configurations were identified using BabyFACS. In the current study, facial configurations were graphed in 5-second epochs for 1-minute post-vaccination and subsequently analyzed for facial expression by time effects using Repeated Measures ANOVAs at each age.

Clear differences in temporal patterns were displayed as infants aged. ANOVA analyses indicated significant facial expression by time interactions at each age.

An important developmental milestone was identified in infants' ability to regulate distress at 6 months. Supporting parents' infant pain management is particularly critical in the first months of life as infants' initial facial expressions appear to be more reflective of an organism overwhelmed by distress. This article is protected by copyright. All rights reserved.

Commentary on "Cognitive Functional Therapy in Patients with Non Specific Chronic Low Back Pain".

Eur J Pain

In this issue you will find a paper by Vibe Fersum et al., entitled "Cognitive Functional Therapy in Patients with Non Specific Chronic Low Back Pa...

Cornea nerve fiber state determines analgesic response to tapentadol in fibromyalgia patients without effective endogenous pain modulation.

Eur J Pain

Tapentadol is a centrally acting analgesic with μ-agonistic activity combined with noradrenaline reuptake inhibition. Its mechanism of action relies on improvement of descending pain inhibition. In the current study, tapentadol's ability to enhance conditioned pain modulation (CPM, an experimental measure of descending pain inhibition) was evaluated in fibromyalgia patients with absent or reduced CPM responses.

A total of 34 fibromyalgia patients completed this double-blind trial. Patients were randomized to receive treatment with tapentadol sustained-release or placebo for a 3-month period with 1-month follow-up. At baseline the cornea nerve fiber state (CNFS) was quantified to determine the presence of nerve fiber pathology and assess its value in the prediction of the analgesic response.

Tapentadol significantly increased CPM responses during treatment with an average increase from baseline of 20.5 ± 12.5% (tapentadol) versus 3.0 ± 11.2% (placebo; p = 0.042). No treatment effect was observed for the absolute pain scores, however analgesia responder rate analyses demonstrated a treatment effect in favor of tapentadol. Pain relief (a reduction in pain score ≥ 30%) was predicted by the presence of a normal CNFS (p = 0.035). Patients with an abnormal CNFS had no analgesic effect from tapentadol despite an increase in CPM.

In chronic pain patients with fibromyalgia, the increase in endogenous pain inhibition by tapentadol was translated into analgesia in patients with a normal CNFS. In those with abnormal CNFS, tapentadol treatment was without analgesic effect. This article is protected by copyright. All rights reserved.

Sándor Márai and his account of painful Guillain-Barré syndrome.

Eur J Pain

Pain is the most frequent sensory symptom of Guillain-Barre syndrome (GBS) but is often underdiagnosed in clinical practice (Pentland & Donald, 199...

Investigating the Causal Mechanisms of Symptom Recovery in Chronic Whiplash Associated Disorders Using Bayesian Networks.

Clin J Pain

The present study's objective is to understand the causal mechanisms underpinning the recovery of individuals with whiplash-associated disorders (WAD). We applied Bayesian Networks (BN) to answer two study aims: (1) to identify the causal mechanism(s) of recovery underpinning neck-specific exercise, and (2) quantify if the cyclical pathway of the fear avoidance model (FAM) is supported by the present data.

We analysed a prospective cohort dataset of 216 individuals with chronic WAD. Fifteen variables were used to build a BN model: treatment group (neck-specific exercise with or without a behavioural approach, or general physical activity), muscle endurance, range of motion, hand strength, neck proprioception, pain catastrophizing, fear, anxiety, depression, self-efficacy, perceived work ability, disability, pain intensity, sex, and follow-up time.

The BN model showed that neck pain reduction rate was greater after neck-specific exercise compared to physical activity prescription (β=0.59 points/month [P<0.001]) only in the presence of two mediators: global neck muscle endurance and perceived work ability. We also found the following pathway of variables that constituted the FAM: anxiety, followed by depressive symptoms, fear, catastrophizing, self-efficacy, and consequently pain.

We uncovered two mediators which explained the mechanisms of effect behind neck-specific exercise, and proposed an alternative FAM pathway. The present study is the first to apply BN modelling to understand the causal mechanisms of recovery in WAD. In doing so, it is anticipated that such analytical methods could increase the precision of treatment in individuals with chronic WAD.

Modulation of Spinal Nociceptive Transmission by Sub-Sensory Threshold Spinal Cord Stimulation in Rats After Nerve Injury.


High-frequency spinal cord stimulation (SCS) administered below the sensory threshold (subparesthetic) can inhibit pain, but the mechanisms remain obscure. We examined how different SCS paradigms applied at intensities below the threshold of Aβ-fiber activation (sub-sensory threshold) affect spinal nociceptive transmission in rats after an L5 spinal nerve ligation (SNL).

Electrophysiology was used to record local field potential (LFP) at L4 spinal cord before, during, and 0-60 min after SCS in SNL rats. LFP was evoked by high-intensity paired-pulse test stimulation (5 mA, 0.2 msec, 400 msec interval) at the sciatic nerve. Epidural SCS was delivered through a miniature electrode placed at T13-L1 and L2-L3 spinal levels. Four patterns of SCS (200 Hz, 1 msec; 500 Hz, 0.5 msec; 1200 Hz; 0.2 msec; 10,000 Hz, 0.024 msec, 30 min, bipolar) were tested at 90% Aβ-threshold as a subthreshold intensity. As a positive control, traditional SCS (50 Hz, 0.2 msec) was tested at 100% Aβ-plateau as a suprathreshold intensity.

Traditional suprathreshold SCS at T13-L1 level significantly reduced LFP to C-fiber inputs (C-LFP). Subthreshold SCS of 200 and 500 Hz, but not 1200 or 10,000 Hz, also reduced C-LFP, albeit to a lesser extent than did traditional SCS (n = 7-10/group). When SCS was applied at the L2-L3 level, only traditional SCS and subthreshold SCS of 200 Hz inhibited C-LFP (n = 8-10/group).

Traditional suprathreshold SCS acutely inhibits spinal nociceptive transmission. Low-frequency subthreshold SCS with a long pulse width (200 Hz, 1 msec), but not higher-frequency SCS, also attenuates C-LFP.

Intrathecal Baclofen Therapy in Patients With Multiple Sclerosis: Improved Outcomes and Reduced Costs Through Identification of Catheter Malfunction.


Two patients previously implanted with intrathecal Baclofen (ITB) pumps for management of intractable spasticity due to multiple sclerosis (MS) were referred to our center for ongoing management of their spasticity. Initial evaluation of these patients revealed high levels of spasticity in the presence of ITB doses 10 times the average daily dose of our other MS patients.

High doses of ITB required frequent clinical visits and result in high drug and procedure costs. Both patients' daily doses were greater than 1000 mcg/day resulting in clinical visits every 1-2 months with drug and procedure costs ranging from 16 to 23 thousand dollars annually based on Medicare national average pricing for physician's office. Of the 59 MS patients receiving ITB therapy at our institution, the mean, median, and mode daily doses for ITB are 184, 115, and 159 mcg/day, respectively. The high ITB doses in these patients and poor spasticity control raised suspicion for pump/catheter malfunction and prompted immediate troubleshooting.

One patient's catheter was found to be disconnected from the pump and the other's catheter tip was outside the intrathecal space. In both cases, the patients were not receiving the therapy. After pump/catheter replacement, both patients received excellent clinical benefits from ITB at significantly lower daily doses. This reduction in dose resulted in decreased frequency of medication refills (twice annually) which resulted in decreased cost of care (12-19 thousand dollars savings annually per patient).

These cases illustrate the need for early ITB pump troubleshooting to identify catheter problems, improve efficacy, and avoid unnecessary healthcare costs.

Redefining Spinal Cord Stimulation "Trials": A Randomized Controlled Trial Using Single-Stage Wireless Permanent Implantable Devices.


"Traditional" spinal cord stimulation (SCS) trials with percutaneous electrodes externalized to a pulse generator (PG) are typically limited in duration due to risk of infection. Newer miniaturized wireless SCS technology eliminates the percutaneous extension (as well as PGs implanted for chronic use), thus facilitating a single-stage implantation after which the device can remain indefinitely.

To evaluate fully implanted wireless SCS devices during a 30-day screening trial in subjects with chronic low back pain and leg pain and a history of lumbosacral spine surgery.

In a randomized controlled trial of single-stage wireless SCS using a wireless percutaneous system, 99 subjects received either 10 kHz high frequency stimulation (HFS) or lower frequency stimulation (LFS) below 1500 Hz (Bolash R, Creamer M, Rauck R, et al. Wireless high frequency spinal cord stimulation (10 kHz) compared to multi-waveform low frequency spinal cord stimulation in the management of chronic pain in failed back surgery syndrome subjects: preliminary results of a multicenter, prospective, randomized controlled study. Pain Med 2019, In this report, we assess the 30-day trial success rate (≥50% pain relief from baseline) and complications.

The overall trial success rate was 88% (87/99): 92% (46/50) for HFS and 84% (41/49) for LFS (NS). The trial success rate in the 64 subjects with predominant low back pain was 92% (59/64) vs. 80% (28/35) in those with leg pain ≥ low back pain (NS). During the screening trial, one infection occurred (1%) and one subject withdrew and was explanted (1%). Electrode migrations were seen on routine follow-up x-rays in 10 cases (10%).

Using wireless SCS devices that allow for an extended trial period and evaluation of various waveforms, we observed a high rate trial success rate with both HFS and LFS waveforms, with minimal incidence of infection. Long-term follow-up will address the cost-effectiveness and morbidity associated with this technology, which facilitates single-stage treatment.

Trends in steroid agent and diluent choices for epidural steroid injections: a survey of Spine Intervention Society physicians.

Regional Anesthesia and Pain Medicine

Epidural steroid injections (ESIs) are a frequently used treatment for refractory radicular spinal pain. ESIs, particularly transforaminal epidural steroid injections (TFESI), may provide pain relief and delay the need for surgery. Corticosteroid agent and diluent choices are known to impact the safety of ESIs. In particular, the risk of embolization with particulate corticosteroids has led to recommendations for non-particulate steroid use by the Multisociety Pain Workgroup. Additionally, there is in vitro evidence that ropivacaine can crystalize in the presence of dexamethasone, potentially creating a particulate-like injectate. Despite widespread use and known risk mitigation strategies, current practice trends related to steroid and diluent choices are unknown.

Identify the use of particulate versus non-particulate corticosteroids for epidural steroid injections in the cervical and lumbar spine, as well as local anesthetics commonly used as diluents during these procedures.

Cross-sectional survey study of 314 physician members of the Spine Interventional Society.

41% and 9% of providers reported using particulate corticosteroids during lumbar TFESIs and cervical TFESI, respectively. Four per cent of providers reported the use of ropivacaine in cervical TFESIs. Forty-four per cent of respondents reported using anesthetic in cervical interlaminar ESIs. 21% of providers report using high volumes (> 4.5 mL) during cervical interlaminar ESIs.

Current trends, as assessed by this survey study, indicate substantial variability in steroid and diluent choice for ESIs. Patterns were identified that may impact patient safety including the continued use of particulate corticosteroids for TFESIs and the use of ropivacaine during TFESIs by a subset of respondents.

Effect of early versus delayed activation of thoracic epidural anesthesia on plasma pro-atrial natriuretic peptide to indicate deviations in central blood volume during esophagectomy.

Regional Anesthesia and Pain Medicine

A side effect to thoracic epidural anesthesia (TEA) is hypotension induced by central hypovolemia. This study addressed whether early activation (EA) versus late activation (LA) of TEA affects plasma pro-atrial natriuretic peptide (proANP) reflecting deviations in the central blood volume (CBV). We hypothesized that EA TEA would reduce plasma proANP, thus reflecting a decrease in CBV.

A randomized, controlled, single-blinded trial was conducted. Patients undergoing open esophagectomy were randomized to EA (n=25, after induction of general anesthesia) or LA TEA (n=25, after re-established gastric continuity) with the epidural catheter placed at the interspaces Th7-8 or Th8-9. Plasma proANP was determined repetitively along with hemodynamic variables and administration of fluid/vasopressors as postoperative complications were noted.

With EA TEA, plasma proANP decreased following induction of anesthesia to the end of surgery (13%; 113±68 to 99±49 pmol/L; p=0.026), but that was not the case in the LA group (3%; 97±44 to 94±49 pmol/L; p=0.565) despite equal fluid balance (+1584±582 vs +1560±563 mL; p=0.888). Accordingly, the EA group required excessive treatment with vasopressors to maintain MAP >60 mm Hg during surgery (2.7±2 vs 1.6±1.4 ephedrine boluses; p=0.033 and infusion of phenylephrine for 216±86 vs 58±91 min; p<0.001). Plasma proANP and fluid balance were correlated only for EA patients (r=0.44; 95% CI 0.04 to 0.91; p=0.033).

EA TEA reduces plasma proANP indicating that CBV becomes affected. Based on a correlation between plasma proANP and fluid balance, a 2000 mL volume surplus of lactated Ringer's solution is required to maintain plasma proANP stable during open esophagectomy.

2014-002036-14 (