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Papers by Lechi Vo

European Journal of Pain, Dec 11, 2022

BackgroundApplying an ice cube to the temple (the conditioning stimulus) inhibits electrically ev... more BackgroundApplying an ice cube to the temple (the conditioning stimulus) inhibits electrically evoked pain in the forearm. The present study aimed to determine whether temple cooling also inhibits pressure‐ and heat‐pain test stimuli in the upper limb and, if so, to investigate the intra‐session test–retest reliability of this response. Additional aims were to establish whether pain inhibition evoked by temple cooling was associated with parasympathetic activity; and to explore sex differences in response.MethodsThe sample consisted of 40 healthy adults (24 females). Heart rate was recorded continuously throughout the session. An ice cube (3 × 4 cm contact area) was applied for 1 min to the temple on the dominant side. Before and immediately afterwards, the pressure pain threshold was measured from the dorsal hand and sensitivity to heat (individually adjusted at baseline to elicit moderate pain) was measured from the ventral forearm. The procedures were repeated 15 min later.ResultsTemple cooling inhibited pressure pain on the hand but not heat pain on the forearm. However, test–retest reliability of pressure pain inhibition was poor. Heart rate decreased during temple cooling, consistent with a “diving” reflex. Males had stronger pressure pain inhibition, lower heart rate and higher overall autonomic activity than females. However, cardiac parasympathetic activation during temple cooling was comparable in both sexes and was unrelated to pain inhibition.ConclusionsThese findings indicate that temple cooling evokes pain inhibition that is stronger in males than in females. Cardiac parasympathetic activity does not appear to mediate this response.SignificanceThe conditioning stimulus in the conditioned pain modulation paradigm is often applied to the upper or lower limbs. This may confound pain‐inhibitory effects in people with peripheral neuropathy who typically have enhanced or diminished sensation in the extremities. Applying an ice cube at the temple area induces pain‐inhibitory effects on the upper limb after the ice is removed. Future research examining pain modulation in people with peripheral neuropathy may consider adopting temple cooling as the conditioning stimulus.

European Journal of Pain, May 29, 2015

ABSTRACT Background In healthy humans, high-frequency electrical stimulation (HFS) of the forearm... more ABSTRACT Background In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only produces hyperalgesia at the site of stimulation but also reduces sensitivity to pressure-pain on the ipsilateral side of the forehead. In addition, HFS augments the ipsilateral trigeminal nociceptive blink reflex and intensifies the ipsilateral component of conditioned pain modulation. The aim of this study was to determine whether α2-adrenoceptors mediate these ipsilateral nociceptive influences.Methods The α2-adrenoceptor antagonist yohimbine was administered to 22 participants in a double-blind, placebo-controlled crossover study. In each session, thermal and mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, the combined effect of HFS and yohimbine on the nociceptive blink reflex and on conditioned pain modulation was explored. In this paradigm, the conditioning stimulus was cold pain in the ipsilateral or contralateral temple, and the test stimulus was electrically evoked pain in the forearm.ResultsBlood pressure and electrodermal activity increased for several hours after yohimbine administration, consistent with blockade of central α2-adrenoceptors. Yohimbine not only augmented the nociceptive blink reflex ipsilateral to HFS but also intensified the inhibitory influence of ipsilateral temple cooling on electrically evoked pain at the HFS-treated site in the forearm. Yohimbine had no consistent effect on primary or secondary hyperalgesia in the forearm or on pressure-pain in the ipsilateral forehead.Conclusions These findings imply involvement of α2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving α2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS.

Diabetic Medicine, Oct 28, 2021

AimsDiabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a ... more AimsDiabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear. There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain.MethodsWe reviewed literature in PubMed published between January 2005 and August 2021.Results and conclusionsIn diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.

Experimental Brain Research, Nov 26, 2013

Vo, L. and Drummond, P.D. (2014) Analgesia to pressure-pain develops in the ipsilateral forehead ... more Vo, L. and Drummond, P.D. (2014) Analgesia to pressure-pain develops in the ipsilateral forehead after highand low-frequency electrical stimulation of the forearm. Experimental Brain Research, 232 (2). pp. 685-693.

The Journal of Pain, Nov 1, 2016

In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes loc... more In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by α 2-adrenoceptor blockade. To determine whether opioid peptides mediate inhibitory effects after HFS, the opioid receptor antagonist naltrexone was co-administered orally with the α 2-adrenoceptor antagonist yohimbine in 16 healthy women in a double-blind placebo-controlled crossover study. In each session, mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, pain ratings to electrical stimulation of HFS-treated or control sites in the forearm were assessed during and after painful stimulation of each temple. Unlike yohimbine alone, the naltrexone + yohimbine combination blocked analgesia evoked by HFS in the ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory effect of pain in the temple on electrically-evoked pain at the HFS-treated site in the forearm. These findings imply involvement of opioid peptides in an ipsilateral analgesic response that complements the more generalized form of conditioned pain modulation. Opioid mediation of this ipsilateral analgesic response appears to override opposing α 2-adrenoceptor effects. Perspective: HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral anti-nociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.

Experimental Brain Research, May 12, 2018

Exposure to moderate levels of ultraviolet B radiation (UVB) is painless but nevertheless induces... more Exposure to moderate levels of ultraviolet B radiation (UVB) is painless but nevertheless induces an inflammatory response that sensitizes primary afferent nociceptors. Subsequently, heating the UVB-treated site can sensitize spinal nociceptors. We used a repeated-measures design to determine whether heating the UVB-treated site also triggers ipsilateral inhibitory controls. Specifically, a 2-cm diameter site on the forearm of 20 participants was exposed to UVB at twice the minimum erythema dose. 48 h later mechanical and thermal sensitivity had increased at the UVB-treated site, indicating primary hyperalgesia. In addition, sensitivity to blunt pressure had increased in the ipsilateral forehead, implying activation of an ipsilateral supra-spinal pro-nociceptive mechanism. Despite this, the area under the curve of the ipsilateral nociceptive blink reflex decreased when the UVB-treated site was heated to induce moderate pain. Together, these findings suggest that the UVB treatment sensitized primary nociceptive afferents and generated an ipsilateral supra-spinal pro-nociceptive mechanism. In addition, sensitization to heat induced by the UVB treatment strengthened an ipsilateral anti-nociceptive process elicited by heat-pain. Infrequent but enduring discharge of sensitized primary nociceptive afferents, driven by inflammation after UVB exposure, might initiate a lateralized supra-spinal pro-nociceptive influence that heightens awareness of impending harm on the sensitized side of the body. In addition, a lateralized anti-nociceptive response triggered by an intense barrage of nociceptive signals may help to differentiate stronger from weaker sources of pain.

Journal of Psychopharmacology, Feb 7, 2017

The R3 component of the electrically evoked blink reflex may form part of a startle reaction. Aco... more The R3 component of the electrically evoked blink reflex may form part of a startle reaction. Acoustic startle responses are augmented by yohimbine, an α2-adrenoceptor antagonist that blocks α2-autoreceptors, and are potentiated by opioid receptor blockade. To investigate these influences on electrically evoked startle responses, 16 mg yohimbine, with (16 participants) or without 50 mg naltrexone (23 participants), was administered in separate double-blind placebo-controlled cross-over experiments. In each experiment, R3 (a probable component of the startle response) was examined before and after high-frequency electrical stimulation of the forearm, a procedure that initiates inhibitory pain controls. Anxiety and somatic symptoms were greater after yohimbine than placebo, and were potentiated by naltrexone. Pain ratings for the electrically evoked startle stimuli decreased after high-frequency electrical stimulation in the placebo session but remained stable after drug administration. Yohimbine with naltrexone, but not yohimbine alone, also blocked an inhibitory effect of high-frequency electrical stimulation on electrically evoked sharp sensations and R3. Together, the findings suggest that adding naltrexone to yohimbine potentiated anxiety and blocked inhibitory influences of high-frequency electrical stimulation on electrically evoked sensations and startle responses. Thus, opioid peptides could reduce activity in nociceptive and startle-reflex pathways, or inhibit crosstalk between these pathways. Failure of this inhibitory opioid influence might be important in chronically painful conditions that are aggravated by startle stimuli.

European Journal of Pain

This is the author's final version of the work, as accepted for publication following peer r... more This is the author's final version of the work, as accepted for publication following peer review but without the publisher's layout or pagination.

Diabetic Medicine, 2021

Scandinavian Journal of Pain, 2021

ObjectivesThe expression of pain in males and females involves complex socio-psychological mechan... more ObjectivesThe expression of pain in males and females involves complex socio-psychological mechanisms. Males may report lower pain to a female experimenter to appear strong, whereas females may report higher pain to a male experimenter to appear weak and to seek protection. However, evidence to support these stereotypes is inconclusive. Individuals who catastrophise about pain rate higher pain than those who do not. How pain catastrophising interacts with the effect of the experimenter’s sex on pain reports is yet to be explored. Thus, the aim of this study was to determine whether pain catastrophising moderated the effect of the experimenter’s sex on pain reports in healthy males and females.MethodsParticipants (n=60, 30 males) were assigned to one of four experimental conditions: males tested by male experimenters, males tested by female experimenters, females tested by male experimenters, and females tested by female experimenters. Participants completed the Pain Catastrophising ...

The Clinical Journal of Pain, 2020

Objectives: In complex regional pain syndrome (CRPS), sensory deficits and/or hyperalgesia often ... more Objectives: In complex regional pain syndrome (CRPS), sensory deficits and/or hyperalgesia often extend beyond the affected limb to encompass other sites on the ipsilateral side of the body. The aim of this study was to determine whether hyperalgesia in the ipsilateral forehead reflects disinhibition and/or sensitization of trigeminal afferent or second-order neurons on the CRPS-affected side. Participants and Methods: To investigate this, blink reflexes to supraorbital electrical stimuli (a 2 mA triple pulse delivered using a concentric electrode) were recorded bilaterally in 30 CRPS patients and 20 controls of similar age and sex distribution. In addition, the effect of acoustic startle stimuli on pain and blink reflexes to supraorbital electrical stimuli was explored. Results: Supraorbital electrical stimulation was more painful on the affected than unaffected side in patients (P<0.05), and was more painful on both sides in patients than controls (P<0.001). In addition, ele...

Experimental Brain Research, 2018

European Journal of Pain, 2015

Background: In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not onl... more Background: In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only produces hyperalgesia at the site of stimulation but also reduces sensitivity to pressure-pain on the ipsilateral side of the forehead. In addition, HFS augments the ipsilateral trigeminal nociceptive blink reflex and intensifies the ipsilateral component of conditioned pain modulation. The aim of this study was to determine whether a 2-adrenoceptors mediate these ipsilateral nociceptive influences. Methods: The a 2-adrenoceptor antagonist yohimbine was administered to 22 participants in a double-blind, placebo-controlled crossover study. In each session, thermal and mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, the combined effect of HFS and yohimbine on the nociceptive blink reflex and on conditioned pain modulation was explored. In this paradigm, the conditioning stimulus was cold pain in the ipsilateral or contralateral temple, and the test stimulus was electrically evoked pain in the forearm. Results: Blood pressure and electrodermal activity increased for several hours after yohimbine administration, consistent with blockade of central a 2-adrenoceptors. Yohimbine not only augmented the nociceptive blink reflex ipsilateral to HFS but also intensified the inhibitory influence of ipsilateral temple cooling on electrically evoked pain at the HFS-treated site in the forearm. Yohimbine had no consistent effect on primary or secondary hyperalgesia in the forearm or on pressure-pain in the ipsilateral forehead. Conclusions: These findings imply involvement of a 2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving a 2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS.

The journal of pain : official journal of the American Pain Society, Jan 4, 2016

European Journal of Pain, 2012

BackgroundIn healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead dur... more BackgroundIn healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high‐frequency electrical stimulation (HFS), which triggers signs of central sensitization.MethodsBefore and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation.ResultsUVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Important...

Vo Lechi Understanding Pain How Is Pain Processed in Healthy Humans Phd Thesis Murdoch University, 2014

This thesis is my own account of my research and contains as its main content work that has not p... more This thesis is my own account of my research and contains as its main content work that has not previously been submitted for a degree at any tertiary education institution.