Biology subjects

Furman, A. J.

Publications and source records attributed to Furman, A. J..

7 recordsLinked to original sources

bioRxiv2024

It's the Sound not the Pulse: Peripheral Magnetic Stimulation Reduces Central Sensitization through Auditory Modulatory Effects

Repetitive peripheral magnetic stimulation (rPMS) is a non-pharmacological, non-invasive analgesic modality with limited side effects. However, there is a paucity of controlled studies demonstrating its efficacy compared to existing pain management tools. Here, in an initial sample of 100 healthy participants (age 18-40), we compared the analgesic efficacy of two rPMS stimulation protocols--continuous theta burst stimulation (ctbPMS) and intermittent TBS (itbPMS)--against transcutaneous electric nerve stimulation (TENS), a peripheral stimulation technique that is commonly used for pain management. We also included a sham rPMS protocol where participants heard the sound of rPMS stimulation while the coil was placed over their arm, but received no peripheral stimulation. We hypothesized that itbPMS and ctbPMS--but not sham--would reduce pain intensity, pain unpleasantness, and secondary hyperalgesia evoked by a phasic heat pain (PHP) paradigm on the volar forearm with similar efficacy to TENS. Neither rPMS nor TENS reduced reported pain intensity or unpleasantness (p>0.25). However, ctbPMS and itbPMS significantly reduced the area of secondary hyperalgesia, whereas TENS did not (F3,96= 4.828, p= 0.004). Unexpectedly, sham rPMS, which involved auditory but no peripheral nerve stimulation, also significantly reduced secondary hyperalgesia compared to TENS. We performed a second study (n=32) to investigate auditory contributions to rPMS analgesia. Masking the rPMS stimulation sound with pink noise eliminated its analgesic effect on secondary hyperalgesia (p=0.5). This is the first study to show that the analgesic properties of rPMS in acute experimental pain may be largely attributed to its auditory component rather than peripheral nerve stimulation.

neuroscience↗

bioRxiv2024

Peak alpha frequency is not significantly altered by five days of experimental pain and repetitive transcranial stimulation of the left dorsolateral prefrontal cortex

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a non-invasive pain treatment. Given the link between individual peak alpha frequency (PAF) of resting-state electroencephalographic recordings and pain sensitivity, and the potential for rTMS to modulate PAF, we investigated these relationships through a secondary analysis of established rTMS-induced analgesia in an experimental model of sustained muscle pain. In a randomised, single-blind, sham-controlled experiment, 30 healthy adults underwent either active (n=15) or sham (n=15) high-frequency rTMS (20 min) to the left dorsolateral prefrontal cortex for five consecutive days following induction of sustained experimental pain by nerve growth factor (NGF) injected into the right extensor carpi radialis brevis muscle. The pain intensity was assessed daily for 14 days on a numerical rating scale (NRS). PAF of the resting state electroencephalography (5 min) was assessed before and one day after the five rTMS treatment days. The pre-registered analysis revealed no significant changes in PAF following five consecutive days of active (from 9.90{+/-}0.39 Hz to 9.95{+/-}0.38 Hz) or sham (from 9.86{+/-}0.44 Hz to 9.81{+/-}0.35 Hz) rTMS, suggesting that the impact of rTMS on NGF-induced pain is independent of PAF modulation. However, exploratory analysis indicated an association between a larger absolute difference in baseline PAF to 10 Hz (i.e. the rTMS frequency) and higher NRS pain ratings at Day 5 in participants receiving active rTMS. This suggests rTMS is more efficient when delivered close to individual PAF or for those with PAF around 10 Hz, necessitating further exploration of PAFs role in rTMS-induced pain relief.

neuroscience↗

bioRxiv2023

Effects of nicotine compared to placebo gum on sensitivity to pain and mediating effects of peak alpha frequency

Recent research has linked individual peak alpha frequency (PAF) to pain sensitivity, but whether PAF alterations can influence pain remains unclear. Our study investigated the effects of nicotine on pain sensitivity and whether pain changes are mediated by PAF changes. In a randomised, double-blind, placebo-controlled experiment, 62 healthy adults (18-44 years) received either 4 mg nicotine (n=29) or placebo gum (n=33). Resting state EEG and pain ratings during prolonged heat and pressure models were collected before and after nicotine intake. The nicotine group showed a small decrease in heat-pain ratings compared to placebo group when controlling confounders, and a small increase in PAF across the scalp from pre- to post-gum, both with and without confounder adjustment. These effects were most pronounced in the central-parietal and right-frontal electrodes. However, mediation analysis did not support the notion that PAF changes mediate nicotines effects on pain sensitivity. While a growing body of literature supports a link between PAF and both acute and chronic pain, further work is needed to understand the mechanisms of this link.

neuroscience↗

bioRxiv2021

Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

The relationship between the 8-12 Hz "alpha: rhythm, the predominant oscillatory activity of the brain, and pain remains unclear. In healthy individuals, acute, noxious stimuli suppress alpha power while patients with chronic pain demonstrate both enhanced alpha power and slowing of the peak alpha frequency (PAF). To investigate these apparent differences, EEG was recorded from healthy individuals while they completed two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two testing visits occurring roughly 8 weeks apart. We report that PAF is reliably slowed and that alpha power is reliably decreased in response to prolonged pain. Furthermore, we show that alpha power changes, but not PAF changes, are fully reversed with stimulus removal suggesting that PAF slowing reflects pain associated states such as sensitization rather than the presence of ongoing pain. Finally, we provide evidence that changes to alpha power and PAF are due to power decreases in the "fast" (10-12 Hz) range of the alpha rhythm. This frequency dependent pain response aligns with the hypothesis that the alpha rhythm is composed of multiple, independent oscillators, and suggest that modulation of a putative "fast" oscillator may represent a promising therapeutic target for treating ongoing pain. In sum, we provide strong evidence that PAF is reliably slowed during prolonged pain and additionally identify a mechanism, "fast" alpha Power, which is responsible for these PAF changes.

neuroscience↗

bioRxiv2020

Cortical 6-9 Hz Oscillation are a Reliable Biomarker of Persistent Pain in Rats

Neural biomarkers of chronic pain offer a potential tool for improving the speed of diagnosis and delivery of treatment for this devastating disease. Here, we tested the hypothesis that pain states are associated with distinct changed in cortical brain waves. We induced neuropathic orofacial pain in female rats by chronic constriction injury of the infraorbital nerve (CCI-ION). In most animals, this resulted in lasting reductions in mechanical sensitivity thresholds, and in lasting increases in facial grimace scores. We recorded electrocortigraphy (ECoG) signals over the neocortex of these rats, before and after CCI-ION, and analyzed these signals with a novel, spectral modelling approach. Consistent with our hypothesis, power in the 6-9 Hz bandwidth of the ECoG was differentially modulated in animals displaying signs of chronic pain. Specifically, development of mechanical hypersensitivity correlated with a decrease in 6-9 Hz power. Furthermore, we show that changes in the power of this oscillation after injury, obtained at the individual animal level, provide a more sensitive marker of pain presence than do traditional between animal comparisons of post-injury oscillatory power. Identification of animals demonstrating chronic-pain behaviors was more accurate when estimates of post-injury oscillatory power were compared against each animals own pre-injury baseline than when compared against post-injury power estimates from animals not developing chronic pain. These results highlight the need for establishing individual-specific, "pain-free" baselines from which oscillation disturbances can be measured and which may constitute a reliable, low-cost approach not only for diagnosing chronic pain, but also for identifying individuals likely to transition from acute to chronic pain.

neuroscience↗

bioRxiv2019

Sensorimotor peak alpha frequency is a reliable biomarker of pain sensitivity

Previous research has observed that individuals with chronic pain demonstrate slower alpha band oscillations (8-12 Hz range) during resting electroencephalography (EEG) than do age-matched, healthy controls. While this slowing may reflect pathological changes within the brain that occur during the chronification of pain, an alternative explanation is that healthy individuals with slower alpha frequencies are more sensitive to prolonged pain, and by extension, more susceptible to developing chronic pain. To formally test this hypothesis, we examined the relationship between the pain-free, resting alpha frequency of healthy individuals and their subsequent sensitivity to two experimental models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two testing visits separated by 8 weeks on average (n = 61 Visit 1, n = 46 Visit 2). We observed that the speed of an individuals pain-free alpha oscillations was negatively correlated with sensitivity to both prolonged pain tests and that this relationship was reliable across short (minutes) and long (weeks) timescales. Furthermore, we used the speed of pain-free alpha oscillations to successfully identify those individuals most sensitive to prolonged pain, which we also validated on data from a separate, independent study. These results suggest that alpha oscillation speed is a reliable biomarker of prolonged pain sensitivity with the potential to become a tool for prospectively identifying pain sensitivity in the clinic.

neuroscience↗

bioRxiv2018

Slow peak alpha frequency and corticomotor depression linked to high pain susceptibility in transition to sustained pain

Mechanisms that predict an individuals susceptibility to pain, before pain is present or in the first few days following pain onset, are unknown. We utilised a clinically-relevant human transitional pain model (intramuscular injections of nerve growth factor) to examine brain mechanisms that predict pain susceptibility. Resting state EEG and corticomotor excitability measured by TMS were evaluated longitudinally in healthy individuals as pain developed and resolved over 21 days. Whereas pre-pain central peak alpha frequency (PAF) correlated with peak pain occurring 4-6 days later, altered corticomotor excitability developed several days after pain onset and showed two distinct patterns (facilitation, depression). Individuals with combined slow PAF and corticomotor depression developed more severe pain. These data provide the first evidence of the temporal profile of key brain mechanisms as pain progressively develops. PAF and corticomotor excitability could represent biomarkers for susceptibility to high pain severity and subsequently, the development of chronic pain.

neuroscience↗