Marcelo Lourenço da Silva

Analgesia Induced by 2- or 100-Hz Electroacupuncture in the Rat Tail-Flick Test Depends on the Activation of Different Descending Pain Inhibitory Mechanisms

UNLABELLED We evaluated the effectiveness of intrathecal antagonists of α1- (WB4101) and α2- (idazoxan) adrenoceptors and serotonergic (methysergide), opioid (naloxone), muscarinic (atropine), GABA(A) (bicuculline) and GABA(B) (phaclofen) receptors in blocking 2- or 100-Hz electroacupuncture (EA)-induced analgesia (EAIA) in the rat tail-flick test. EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints in lightly anesthetized rats. EA increased tail-flick latency, where the effect of 2-Hz EA lasted longer than that produced by 100-Hz EA. The 2-Hz EAIA was inhibited by naloxone or atropine, was less intense and shorter after WB4101 or idazoxan, and was shorter after methysergide, bicuculline, or phaclofen. The 100-Hz EAIA was less intense and shorter after naloxone and atropine, less intense and longer after phaclofen, shorter after methysergide or bicuculline, and remained unchanged after WB4101 or idazoxan. We postulate that the intensity of the effect of 2-Hz EA depends on noradrenergic descending mechanisms and involves spinal opioid and muscarinic mechanisms, whereas the duration of the effect depends on both noradrenergic and serotonergic descending mechanisms, and involves spinal GABAergic modulation. In contrast, the intensity of 100-Hz EAIA involves spinal muscarinic, opioid, and GABA(B) mechanisms, while the duration of the effects depends on spinal serotonergic, muscarinic, opioid, and GABA(A) mechanisms. PERSPECTIVE The results of this study indicate that 2- and 100-Hz EA induce analgesia in the rat tail-flick test activating different descending mechanisms at the spinal cord level that control the intensity and duration of the effect. The adequate pharmacological manipulation of such mechanisms may improve EA effectiveness for pain management.

The integrity of the anterior pretectal nucleus and dorsolateral funiculus is necessary for electroacupuncture-induced analgesia in the rat tail-flick test

Previous studies have indicated that the anterior pretectal nucleus (APtN) is implicated in pathways that descend through the dorsolateral funiculus (DLF) to modulate nociceptive inputs in the spinal dorsal horn. The activation of descending inhibitory mechanisms also seems to be involved in electroacupuncture (EA)‐induced analgesia. This study utilized the tail‐flick test to examine the changes produced by DLF lesion or injection of 2% lidocaine into the APtN in the analgesia induced by 2 or 100 Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints in lightly anesthetized rats. Tail‐flick latency was significantly increased by EA, the effect of 2 Hz EA lasting longer than that produced by 100 Hz EA. The effect of either 2 or 100 Hz EA did not occur in DLF lesion rats. The effect of 2 Hz EA did not occur in rats with neural block of the whole or dorsal APtN. In contrast, the effect of 100 Hz EA was reduced in rats with neural block of the whole APtN, but remained unchanged in rats with neural block of the dorsal APtN. We thus conclude that the integrity of the APtN and DLF is necessary for EA‐induced analgesia in the rat tail‐flick test. In addition, the integrity of the dorsal APtN is necessary for the analgesic effect of 2 but not 100 Hz EA.

The antinociceptive effect of electroacupuncture at different depths of acupoints and under the needling surface

BackgroundThe stimulation of acupoints along the meridians, but not the non-acupoints outside of the meridians, produces analgesia. Although the acupoint is defined at the body surface, the exact location of the acupoints is not known. This study aims to examine whether the intensity and duration of the analgesic effect of electroacupuncture (EA) at the Zusanli (ST36) and Sanynjiao acupoints (SP6) change according to the depth of the stimulation.MethodsNinety-six male Wistar rats classified as responders were arbitrarily allocated into 16 groups of six rats each. Six groups received EA with uninsulated acupuncture needles (type I) or needles that were immersed in varnish and had the varnish circularly peeled 0.2 mm from the tip (type II), 0.2 mm at 3 mm (type III) or 5 mm (type IV) from the tip, or 0.2 mm at 5 and 1 mm from the tip (type V), or EA sham for 20 min. Five groups received injection of formalin into the acupoint bilaterally at 5 mm or 1 mm deep into ST36, 5 mm below ST36 but inserting the needle at 45° to the skin surface, or 5 mm deep into non-acupoints. The remaining groups received intraplantar injection of saline, 1% or 2.5% formalin. The analgesic effects were measured by the rat tail-flick test.ResultsThe bilateral stimulation of ST36 and SP6 by uninsulated or insulated needles produced analgesia in the rat tail-flick test. The stronger and longer lasting effects occurred after EA with the types I and V needles, or injection of formalin 5 mm deep into ST36. The remaining needles produced weaker and shorter lasting effects. Slow analgesic effect also occurred after formalin injection at 1 mm or 5 mm below ST36 by inserting the needle at 45° to the skin surface.ConclusionThe experimental results suggest that the efficacy of the EA stimulation depends on the spatial distribution of the current density under the needling surface rather than only the acupoint or the depth of needling.

The combined effect of acupuncture and Tanacetum parthenium on quality of life in women with headache: randomised study

Background The aim of the present study was to investigate the efficacy and tolerability of acupuncture (AC), Tanacetum (TAN) or combined treatment on quality of life in women with chronic migraine (CM). Methods A total of 69 women volunteers were randomly divided into 3 groups: AC, acupuncture administered in 20 sessions over 10 weeks (n=22); TAN, at 150 mg/day (n=23); and AC+TAN (n=23). The primary outcome was Short-Form 36 (SF-36) quality of life assessment score. Secondary outcomes included the Migraine Disability Assessment (MIDAS) and visual analogue scale (VAS) score experienced after randomisation. Results AC+TAN was statistically significantly more effective than AC or TAN alone in overall health-related quality of life (SF-36; p<0.05), on MIDAS score (−35.1 (10.6) AC vs −24.8 (11.7) TAN vs −42.5 (9.8) AC+TAN; p<0.05) and in reducing the mean score of pain on VAS (−5.6 (2.4) AC vs −3.7 (2.1) TAN vs −6.4 (3.1) AC+TAN; p<0.05). Conclusions The present work shows an improvement of the quality of life and better analgesic effect of acupuncture combined with TAN treatment on migraine pain in women when compared with acupuncture or TAN alone.

Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the anterior pretectal nucleus.

AIMS The anterior pretectal nucleus (APtN) and electroacupuncture (EA) activate descending mechanisms to modulate nociceptive inputs in the spinal dorsal horn. This study examines qualitatively whether mechanisms in the APtN participate in the EA-induced analgesia in rats. MAIN METHODS The tail-flick test was utilized to examine the changes produced by non-selective antagonists of serotonergic (methysergide, 37 pg), muscarinic (atropine, 10 ng) and opioid (naloxone, 10 ng) receptors; selective antagonists against μ (CTOP, 6.4 μg), δ (ICI174,864, 6.9 μg) or κ (nor-BNI, 7.3 μg); 5HT1 (methiothepin, 0.47 μg), 5HT2 (ketanserin, 5.4 μg), or 5HT3 (MDL 72222, 15.7 μg); and GABAA (bicuculline, 150 ng) receptors injected into the dorsal (d) or ventral (v) APtN on the antinociception induced by a 20-min EA applied at 2- or 100-Hz frequency to the Zusanli and Sanyinjiao acupoints. KEY FINDINGS The 2-Hz EA-induced analgesia was blocked by naloxone, CTOP or atropine, was less intense after bicuculline, was shorter after methysergide or methiothepin in dAPtN, and was less intense after methysergide, methiothepin and bicuculline in vAPtN. The 100-Hz EA-induced analgesia was less intense after methysergide, methiothepin and CTOP in vAPtN, and remained unchanged after injection of the antagonists into the dAPtN. SIGNIFICANCE The 2-Hz EA-induced analgesia utilizes cholinergic muscarinic, μ-opioid, GABAA and 5-HT1 mechanisms in the dAPtN and μ-opioid and 5-HT1 mechanisms in the vAPtN, while 100-Hz EA-induced analgesia utilizes μ-opioid and 5-HT1 mechanisms in the vAPtN but does not utilize them in the dAPtN.

Retrosplenial Cortex is Involved in Analgesia Induced by 2- but not 100-Hz Electroacupuncture in the Rat Tail-Flick Test

This study examined whether or not the antinociceptive effect of 2- or 100-Hz electroacupuncture (EA) depends on the integrity of the retrosplenial cortex (RSC). Rats were taken for determination of tail-flick latency before and after injection of saline or 2% lidocaine (0.25 μl) into the retrosplenial cortex (RSC) bilaterally. Five minutes later, they were submitted to a 20-minute period of 2 Hz, 100 Hz, or sham EA at the Zusanli and Sanyinjiao acupoints bilaterally, and tail-flick latency was measured within 30 seconds after the end of stimulation and at 5-minute intervals for up to 30 minutes. EA at a frequency of either 2 or 100 Hz induced a strong and long-lasting inhibition of the tail-flick reflex in rats treated with saline (0.25 μl) injected into the RSC. The analgesia produced by 2-Hz EA lasted for a shorter time in lidocaine-treated rats. By contrast, RSC impairment did not change the analgesic effect of 100 Hz EA. The integrity of the RSC is implicated in the duration of analgesia induced by low-frequency EA but is not essential for the analgesic effects evoked by high-frequency EA.

Electroacupuncture at 2/100 hz activates antinociceptive spinal mechanisms different from those activated by electroacupuncture at 2 and 100 hz in responder rats.

We examined the effects of intrathecal injection of desipramine and fluoxetine (selective inhibitors of norepinephrine and 5-HT uptake, resp.), thiorphan and neostigmine (inhibitors of enkephalinase and acetylcholinesterase, resp.), gabapentin (a GABA releaser), and vigabatrin (an inhibitor of GABA-transaminase) on the antinociception induced by 2 Hz, 100 Hz, or 2/100 Hz electroacupuncture (EA) applied bilaterally to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints using the rat tail-flick test. We show that 2 Hz EA antinociception lasts longer after the administration of drugs that increase the spinal availability of norepinephrine, acetylcholine, or GABA; 100 Hz EA antinociception lasts longer after drug that increases the spinal availability of norepinephrine; 2/100 Hz EA antinociception lasts longer after drugs that increase the spinal availability of endogenous opioids or GABA. We conclude that the antinociceptive effect of 2/100 Hz EA is different from the synergistic effect of alternate stimulation at 2 and 100 Hz because the effect of the former is not changed by increasing the spinal availability of serotonin and lasts longer after the administration of vigabatrin. The combination of EA with drugs that increase the availability of spinal neurotransmitters involved in the modulation of nociceptive inputs may result in a synergistic antinociceptive effect in the rat tail-flick test.

Antinociceptive effects of low-level laser therapy at 3 and 8 j/cm2 in a rat model of postoperative pain: possible role of endogenous Opioids

Low‐level laser therapy (LLLT) is the direct application of light to stimulate cell responses (photobiomodulation) to promote tissue healing, reduce inflammation, and induce analgesia; the molecular basis for these effects of LLLT remains unclear. The objective of this study was to evaluate the analgesic effect of LLLT in the rat plantar incision model of postoperative pain as well as to investigate some of the possible mechanisms involved in this effect. Wistar rats were submitted to plantar incision and treated with LLLT (830 nm, continuous‐mode, 30 mW/cm2, 1–12 J/cm2). Postoperative thermal and mechanical hypersensitivity were monitored for 24 hours post‐incision. In addition, the animals were pretreated with saline, naloxone (a nonselective opioid receptor antagonist; 20 µg/5 µl) or methysergide (5‐HT2C, 5‐HT2A, 5‐HT7, 5‐HT5a, 5‐HT6, and 5‐HT1F receptors antagonist; 30 µg/5 µl). Moreover, 24 hours after incision and treatment, the TNF‐α and IL‐1β levels in serum were evaluated. Our results demonstrate, for the first time, that LLLT at 3 or 8 J/cm2, but not at 1–2, 4–7, or 9–12 J/cm2, induced an analgesic effect on postoperative pain. Naloxone, but not methysergide, blocked the LLLT‐induced anti‐nociceptive effect. Additionally, IL‐1‐β and TNF‐α production significantly decreased after LLLT at 3 or 8 J/cm2. Our results suggest that LLLT at 3 or 8 J/cm2 primarily modulates the endogenous opioids system and is not directly mediated by serotonergic receptors. Reduction of IL‐1β and TNF‐α may play a role in the antinociceptive action of LLLT. Lasers Surg. Med. 49:844–851, 2017.

Experiencing early life maternal separation increases pain sensitivity in adult offspring

Maternal separation is a widely accepted model for studying long‐term behavioral changes produced by events during early life and its association with changes in pain sensitivity. Thus, our objective was to evaluate sensitivity to pain, under different stimuli in adult male and female rats that had undergone early life maternal separation. Animals were subjected to maternal separation from postnatal day (PND) 2–15. Maternal behavior and litter weight were evaluated during this period. Sensitivity to pain was assessed in offsprings during adulthood by exposing them to stimuli, including formalin (5%; 20 μl), a hot plate, and the electronic von Frey test, 4, 7, 10, and 24 h after the administration of saline or Freunds complete adjuvant (CFA) injection. Maternal separation did not affect maternal behavior or litter weight during PND 2–15. However, experiencing maternal separation increased pain sensitivity in the rats subjected to formalin by increasing number of flinches and licking time Further, females appeared more sensitive than males to thermal stimuli, as they showed a decrease in latency in the hot plate test. In this test, male and female offsprings that were exposed to early life maternal separation and received the CFA injection also showed a reduction in latency to react to the painful stimuli. In the von Frey test, there was a reduction in withdrawal threshold in maternal separation animals injected with CFA, thus demonstrating a greater sensitivity to the mechanical stimuli. In conclusion, experiencing early life maternal separation increased pain sensitivity in adult offsprings. Thus, our data are important to understand the impact of environmental influences, such as stressful life events during critical developmental periods, on pain vulnerability.

Prevalence and characteristics of chronic pain in Brazil: a national internet-based survey study

BACKGROUND AND OBJECTIVES: The prevalence of chronic pain has been increasing in the world, and it is considered the most underestimated health care problem impacting the quality of life. Furthermore, there is little consensus regarding the burden of chronic pain in Brazil. The present study aimed to investigate the prevalence of chronic pain in the general Brazilian adult population, and the socio-demographic, clinical, medical conditions and pain locations on the body. METHODS: A cross-sectional Internet-based survey was conducted in a nationally representative sample of Brazil adults to estimate the prevalence, sociodemographic correlates and characteristics of chronic pain in the Brazilian population. Twenty-seven-thousand and three hundred forty-five (27,345) representative residents were contacted. RESULTS: From 27,345 individuals, 20,830 (76.17%) presented chronic, recurrent, or long-lasting pain, lasting for at least 6 months. Nearly half of the respondents were 65 years older (48.15%) and the prevalence was higher in females (84,60%) than males (16.40%). The prevalence of primary chronic lower back pain was 59.85%; of primary rheumatoid arthritis was (59.78%) and primary osteoarthritis pain was 69.02%. Half of the respondents with chronic pain experienced daily pain, and average (past 3 months) pain intensity was moderate at 57.28%. CONCLUSION: Chronic pain affects more than two-thirds of the population of Brazil. Our findings revealed a high prevalence and severity of chronic pain and suggested that it is a public health problem in Brazil. Risk factors are being a woman, advanced age and low levels of household income. There is a need for improved health policies in Brazil for patients with chronic pain.