No study has reported a unilateral localized cerebral lesion of the posterior insula bilaterally reducing noxious stimuli perception. A 57-year-old man with an infarct involving the right posterior ...insula presented with reduced somatosensory response in the upper and lower left extremities. Furthermore, there was a reduced response to noxious stimulation in the right upper and lower limbs. We noted reductions in pain, noxious heat and cold perceptions, and sensitivity to increasing temperature. Other somatic sensations, including non-noxious temperatures, remained intact in the right upper and lower extremities. These findings in our patient with a unilateral insular lesion indicated a bilaterally reduced perception of noxious stimulation.
The parasitoid wasp
Ampulex compressa
envenomates the brain of its host the American cockroach (
Periplaneta americana
), thereby making it a behaviorally compliant food supply for its offspring. The ...target of venom injection is a locomotory command center in the brain called the central complex. In this study, we investigate why stung cockroaches do not respond to injuries incurred during the manipulation process by the wasp. In particular, we examine how envenomation compromises nociceptive signaling pathways in the host. Noxious stimuli applied to the cuticle of stung cockroaches fail to evoke escape responses, even though nociceptive interneurons projecting to the brain respond normally. Hence, while nociceptive signals are carried forward to the brain, they fail to trigger robust nocifensive behavior. Electrophysiological recordings from the central complex of stung animals demonstrate decreases in peak firing rate, total firing, and duration of noxious-evoked activity. The single parameter best correlated with altered noxious-evoked behavioral responses of stung cockroaches is reduced duration of the evoked response in the central complex. Our findings demonstrate how the reproductive strategy of a parasitoid wasp is served by venom-mediated elimination of aversive, nocifensive behavior in its host.
Izhodišča: Boleče izkušnje imajo v obdobju novorojenčka škodljive kratkoročne in dolgoročne posledice. Zato je izredno pomembna pravočasna prepoznava in zdravljenje bolečine. Metoda merjenja ...prevodnosti kože je novejša, neinvazivna in objektivna metoda merjenja bolečine, ki zrcali avtonomni odziv na stres ali bolečino. Namen raziskave je bil opredeliti klinični pomen in uporabnost nadzora nocicepcije z merjenjem prevodnosti kože pri bolnih novorojenčkih, izpostavljenih bolečinskim dražljajem.
Metode: V prospektivno študijo je bilo vključenih 35 novorojenčkov, zdravljenih na Kliničnem oddelku za neonatologijo Pediatrične klinike UKC Ljubljana med 1. 10. 2020 in 30. 04. 2021. Opravljene so bile meritve fizioloških parametrov, ocene po lestvicah NIPS, NPASS in meritve prevodnosti kože 5 minut pred, med in 5 minut po bolečinskem dražljaju. Za analizo je bila uporabljena Friedmanova dvosmerna analiza variance rangov s post hoc preizkusi, Mann-Whitney U preizkus in logistična regresija.
Rezultati: Prevodnost kože se je med bolečinskim dražljajem pomembno spremenila v primerjavi z vrednostmi pred bolečinskim dražljajem in po njem (p=0,000, p=0,000), prav tako srčna frekvenca (p=0,000, p=0,000), nasičenost hemoglobina s kisikom (p=0,021, p=0,012) in seštevka točk po lestvicah NIPS (p=0,000, p=0,00) in NPASS (p=0,000, p=0,000). Frekvenca dihanja se med bolečinskim dražljajem ni pomembno spremenila v primerjavi z meritvami pred dražljajem in po njem (p=0,098). Največjo ploščino pod krivuljo ROC je imela lestvica NPASS 0,987 95 % IZ 0.969, 1, najmanjšo pa število vrhov na sekundo 0,869 95 % IZ 0.780, 0.958.
Zaključki: Spremembe prevodnosti kože se ujemajo s spremembami fizioloških parametrov in ocenami po lestvicah za ocenjevanje bolečine. Metode merjenja bolečinskega odziva različno dobro napovejo bolečinski dražljaj.
Topical refrigerant spray is commonly used with routine hand injections despite mixed evidence about its efficacy in reducing the pain experience. We hypothesize that the use of topical refrigerant ...spray decreases the pain experience of an instantaneous noxious stimulus.
Eighty adult volunteer participants were enrolled in the study. We constructed an instrument using the smooth end of a Kirschner wire mounted to the spring of a ballpoint pen to apply an instantaneous noxious stimulus to the long (middle) finger proximal nail fold. Participants completed two trials and were randomized to receive the topical refrigerant spray before either the first or second stimulus and on either the left or right side. Participants were asked to rate the pain of each experience using an 11-point Likert scale and indicate which condition they preferred, if any.
The mean pain ratings for the spray and no-spray conditions were 2.0 and 4.3, respectively, giving a mean difference of −2.3 (P < .001, α = 0.05). Subgroup analysis showed no significant effect of sex or medical versus nonmedical occupation (P = .28 and .11 respectively) on the mean difference in pain rating between the two conditions. Participants who received the spray first had a higher mean difference in pain rating (2.7) than that in those who received it second (1.9). Fifty-nine participants preferred the spray, whereas 21 participants either preferred no spray or had no preference (P < .0001).
The use of topical refrigerant spray significantly decreased the perception of pain from an instantaneous noxious stimulus. A significant majority of participants also preferred the topical refrigerant spray condition. The use of topical refrigerant spray for painful procedures, such as needle insertions, may improve the overall patient experience.
Therapeutic I.
•Navanax attack sensitized Aplysia reflex withdrawal.•Short-term sensitization was site-specific, stronger at the anatomical point of attack.•Paradoxically, long-term sensitization after head attack ...was not observed in head withdrawal, but only in tail withdrawal.
Neurobiological studies of the model species, Aplysia californica (Mollusca, Gastropoda, Euopisthobranchia), have helped advance our knowledge of the neural bases of different forms of learning, including sensitization, a non-associative increase in withdrawal behaviors in response to mild innocuous stimuli. However, our understanding of the natural context for this learning has lagged behind the mechanistic studies. Previous studies, which exclusively used artificial stimuli, such as electric shock, to produce sensitization, left open the question of which stimuli might cause sensitization in nature. Our laboratory first addressed this question by testing for short and long-term sensitization after predatory attack by a natural predator, the spiny lobster. In the present study, we tested for sensitization after attack by a very different predator, the predacious sea-slug, Navanax inermis (Mollusca, Gastropoda, Euopisthobranchia).
Unlike the biting and prodding action of lobster attack, Navanax uses a rapid strike that sucks and squeezes its prey in an attempt to swallow it whole. We found that Navanax attack to the head of Aplysia caused strong immediate sensitization of head withdrawal, and weaker, delayed, sensitization of tail-mantle withdrawal. By contrast, attack to the tail of Aplysia resulted in no sensitization of either reflex. We also developed an artificial attack stimulus that allowed us to mimick a more consistently strong attack. This artificial attack produced stronger but qualitatively similar sensitization: Strong immediate sensitization of head withdrawal and weaker sensitization of tail-mantle withdrawal after head attack, immediate sensitization in tail-mantle withdrawal, but no sensitization of head withdrawal after tail attack. We conclude that Navanax attack causes robust site-specific sensitization (enhanced sensitization near the site of attack), and weaker general sensitization (sensitization of responses to stimuli distal to the attack site).
We also tested for long-term sensitization (lasting longer than 24 h) after temporally-spaced delivery of four natural Navanax attacks to the head of subject Aplysia. Surprisingly, these head attacks, any one of which strongly sensitizes head withdrawal in the short term, failed to sensitize head-withdrawal in the long term. Paradoxically, these repeated head attacks produced long-term sensitization in tail-mantle withdrawal.
These experiments and observations confirm that Navanax attack causes short, and long-term sensitization of withdrawal reflexes of Aplysia. They add site-specific sensitization as well as paradoxical long-term sensitization of tail-mantle withdrawal to a short list of naturally induced learning phenotypes in this model species. Together with previous observations of sensitization after lobster attack, these data strongly support the premise that sensitization in Aplysia is an adaptive response to sub-lethal predator attack.
No study has reported a unilateral localized cerebral lesion of the posterior insula bilaterally reducing noxious stimuli perception. A 57-year-old man with an infarct involving the right posterior ...insula presented with reduced somatosensory response in the upper and lower left extremities. Furthermore, there was a reduced response to noxious stimulation in the right upper and lower limbs. We noted reductions in pain, noxious heat and cold perceptions, and sensitivity to increasing temperature. Other somatic sensations, including non-noxious temperatures, remained intact in the right upper and lower extremities. These findings in our patient with a unilateral insular lesion indicated a bilaterally reduced perception of noxious stimulation.
The skin conductance algesimeter (SCA) reflects the sympathetic nervous system influenced by changes in emotions, which releases the acetylcholine that acts on muscarine receptors, causing a ...subsequent burst of sweat and increased skin conductance. The SCA reacts immediately and is not influenced by hemodynamic variability or neuromuscular blockade. The use of SCA for pain and nociceptive assessment is outlined in this review.
When pain was monitored by verbal reporting in postoperative patients, the SCA had a sensitivity of about 90% and specificity up to 74% to identify the pain, better than heart rate and blood pressure. In general anesthetized patients, both the sensitivity and specificity were about 90% to detect responses to noxious stimulation when compared with clinical stress variables. The SCA reflects changes in norepeinephrine levels induced by nociception better than heart rate, blood pressure, and electroencephalograph (EEG) monitors. Unlike EEG monitors, the SCA response is sensitive to experimental noxious stimuli during general anesthesia, and the measured response was attenuated by analgesic medication. This SCA response is significantly associated with genetically modulated pain sensitivity. Moreover, noxious stimuli in artificially ventilated patients and in preterm infants increase the SCA index, and the increase correlates to the clinical discomfort.
The SCA detects nociceptive pain fast and continuously, specific to the individual, with higher sensitivity and specificity than other available objective methods.
This prospective blinded randomized study aimed to determine whether the timing of morphine and phenylbutazone administration affects the breathing response to skin incision, recovery quality, ...behavior and cardiorespiratory variables in horses undergoing fetlock arthroscopy.Ten Standardbred horses were premedicated with acepromazine (0.04 mg kg-1 IM) and romifidine (0.04 mg kg-1 IV). Anesthesia was induced with diazepam (0.05 mg kg-1) and ketamine (2.2 mg kg-1) IV at T0. Horses in group PRE (n = 5) received morphine (0.1 mg kg-1) and phenylbutazone (2.2 mg kg-1) IV after induction and an equivalent amount of saline after surgery. Horses in group POST (n = 5) received the inversed treatment. Anesthesia was maintained with isoflurane 2% in 100% oxygen. Hypotension (mean arterial pressure < 60 mmHg) was treated with dobutamine. All horses breathed spontaneously. Dobutamine requirements, respiratory rate (fR), heart rate (HR), mean arterial blood pressure, end tidal CO2, inspired (i) and expired (e) tidal and minute volume (VT and V̇E), inspiratory time (IT) and the inspiratory gas flow (VTi/IT) were measured every five minutes. Data were averaged during four 15 minutes periods before (P1, P2) and after the incision (P3, P4). Serial blood-gas analyses were also performed. Recoveries were unassisted, video-recorded and scored by three anesthetists blinded to the treatment. The post-operative behavior of the horses (25 demeanors), HR and fR were recorded at three time points before induction (T0-24h, T0-12h, and T0-2h) and six time points after recovery (TR) (TR+2, 4, 6, 12, 24, 48 h).Data were compared between groups using a Wilcoxon test and within groups using a Friedman test or a Kruskal-Wallis signed rank test when applicable.Tidal volumes (VTe and VTi) were higher in PRE than in POST during all the considered periods but the difference between groups was only significant during P2 (VTe in ml kg-1 in PRE: 13 9, 15, in POST: 9 8,9, p = 0.01). None of the other variables were significantly different between and within groups. Under our experimental conditions, skin incision did not affect respiratory variables. Administration of pre- versus post-operative phenylbutazone and morphine did not influence recovery quality, HR or fR
Some anesthetic agents or adjunct medications administered during general anesthesia can cause an accelerated idioventricular rhythm (AIVR), which is associated with higher vagal tone and lower ...sympathetic activity. We encountered AIVR induced by vagal response to injection-related pain following local anesthetic infiltration into the oral mucosa during general anesthesia. A 48-year-old woman underwent extraction of a residual tooth root from the left maxillary sinus under general anesthesia. Routine preoperative electrocardiogram (ECG) was otherwise normal. Eight milliliters of 1% lidocaine (80 mg) with 1:100,000 epinephrine (80 μg) was infiltrated around the left maxillary molars over 20 seconds using a 23-gauge needle and firm pressure. Widened QRS complexes consistent with AIVR were observed for ∼60 seconds, followed by an atrioventricular junctional rhythm and the return of normal sinus rhythm. A cardiology consultation and 12-lead ECG in the operating room produced no additional concerns, so the operation continued with no complications. AIVR was presumably caused by activation of the trigeminocardiac reflex triggered by intense pain following rapid local anesthetic infiltration with a large gauge needle and firm pressure. Administration of local anesthetic should be performed cautiously when using a large gauge needle and avoid excessive pressure.
To test the postexposure analgesic efficacy of low doses of eugenol in zebrafish.
Prospective experimental study.
A total of 76 large adult zebrafish (Danio rerio).
Fish swimming behavior (median ...velocity, freeze time, high-speed swimming and distance moved in the vertical direction) was recorded in a 1.6 L video arena before and after exposure to eugenol (0, 1, 2, 5, 10 and 20 mg L
). In a second experiment, fish were anesthetized with 2-phenoxy-ethanol and treated with an injection of 5% acetic acid (noxious stimulus), and then exposed to 0, 1, 2 and 5 mg L
eugenol. The fish swimming behavior was also recorded.
The higher doses (10 and 20 mg L
) reduced the median velocity, high-speed swimming and distance moved in the vertical direction, and increased the freeze time. Zebrafish behavior was not altered by eugenol (1, 2 and 5 mg L
) after noxious stimulation.
The change in the behavior of zebrafish associated with a noxious stimulus can be monitored and is a good model for studying analgesia in fish. Eugenol (10 and 20 mg L
) induced zebrafish sedation. The response after a noxious stimulus was not affected by postexposure to lower doses, and thus we cannot recommend its use as an analgesic.