Effects of repetitive pinprick stimulation on preterm offspring: Alterations in nociceptive responses and inflammatory hypersensitivity in adulthood.

INTRODUCTION: This study investigates the effects of repetitive pinprick stimulation on preterm offspring and its impact on nociceptive responses and inflammatory hypersensitivity in adulthood. OBJECTIVES: The objective is to shed light on the potential long-term consequences of neonatal pain and prematurity on sensory processing. METHODS: Term and preterm rats were subjected to repetitive pinprick (PP) stimulation or control (CC) during the neonatal period. Adult rats received CFA injection to induce inflammatory hypersensitivity, and mechanical hypersensitivity was measured. Gender differences in inflammatory hypersensitivity were also examined. Maternal behavior, litter weight, and offspring growth were monitored to assess any potential influences of the stimulation on these parameters. RESULTS: In preterm rats, the PP stimulation did not affect baseline thresholds to mechanical stimuli, but increased mechanical hypersensitivity after CFA injection in adult rats. Females exhibited greater inflammatory hypersensitivity compared to males. Maternal behavior, litter weight, and offspring growth were not influenced by the stimulation. PP stimulation during the neonatal period led to changes in nociceptive responses in adulthood, potentially altering sensory processing. CONCLUSION: PP stimulation in preterm rats during the neonatal period resulted in changes in nociceptive responses in adulthood, leading to increased inflammatory hypersensitivity. The study emphasizes how early development can significantly impact sensory processing and further highlights the potential long-term consequences of prematurity and neonatal pain on this processing.

Evaluation of the nociceptive threshold and inflammatory markers in rats after induction of pulmonary emphysema by elastase in the phasic, inflammatory and neuropathic pain models / Avaliação do limiar nociceptivo e marcadores inflamatórios em ratos após indução de enfisema pulmonar por elastase nos modelos de dor fásica, inflamatória e neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction, although it compromises the lungs, it also produces significant systemic consequences. The objective of this study was to analyze the relationship between pro-inflammatory cytokines and nociceptive threshold in rats with porcine pancreatic elastase-induced COPD. METHODS 144 animals were randomly distributed into 3 different models: nociceptive phasic pain at tail-flick test (TF), inflammatory pain in the Freund's complete adjuvant model (CFA) and neuropathic pain in the sciatic nerve constriction model (CCI). 21 days after tracheal instillation of elastase the COPD was established, and the nociceptive threshold was evaluated at different times. RESULTS: The animals with COPD in TF had a shorter latency time and higher levels of IL-1b, IL-6 and TNF-alpha cytokines. In the CFA and CCI model, the animals with COPD showed an increase in the mechanical hyperalgesia and the levels of IL-1b, IL-6 and TNF-alpha were greater in plasma up to 24 hours. CONCLUSION: Animals with COPD have higher levels of pro-inflammatory cytokines and reduced nociceptive thresholds, suggesting a relationship between COPD and increased nociception.

RESUMO JUSTIFICATIVA E OBJETIVOS: A doença pulmonar obstrutiva crônica (DPOC) caracteriza-se pela obstrução do fluxo aéreo e, embora comprometa os pulmões, produz importantes consequências sistêmicas. O objetivo deste estudo foi analisar a relação entre citocinas pró-inflamatórias e limiar nociceptivo em ratos com DPOC induzida por elastase pancreática suína. MÉTODOS: Cento e quarenta e quatro animais foram distribuídos aleatoriamente em três modelos diferentes: dor fásica nociceptiva no teste de retirada de cauda (TF), dor inflamatória no modelo de adjuvante completo de Freund (CFA) e dor neuropática no modelo de constrição do nervo ciático (CCI). Vinte e um dias após a instilação traqueal de elastase a DPOC foi estabelecida e o limiar nociceptivo foi avaliado em diferentes períodos. RESULTADOS: Os animais com DPOC apresentaram menor tempo de latência de retirada e maiores níveis das citocinas IL-1β, IL-6 e TNF-alfa no T F. No modelo CFA e CCI, os animais com DPOC apresentaram aumento da hiperalgesia mecânica e os níveis de IL-1β, IL-6 e TNF-alfa foram maiores no plasma até 24 horas. CONCLUSÃO: Animais com DPOC apresentam níveis mais elevados de citocinas pró-inflamatórias e limiares nociceptivos reduzidos, sugerindo uma relação entre DPOC e aumento da nocicepção.

Electroacupuncture modulates cortical excitability in a manner dependent on the parameters used.

INTRODUCTION: There is evidence that electroacupuncture (EA) acts through the modulation of brain activity, but little is known about its influence on corticospinal excitability of the primary motor cortex (M1). OBJECTIVE: To investigate the influence of EA parameters on the excitability of M1 in healthy individuals. METHODS: A parallel, double blind, randomized controlled trial in healthy subjects, evaluating the influence of an EA intervention on M1 excitability. Participants had a needle inserted at LI4 in the dominant hand and received electrical stimulation of different frequencies (10 or 100 Hz) and amplitude (sensory or motor threshold) for 20 min. In the control group, only a brief (30 s) electrical stimulation was applied. Single and paired pulse transcranial magnetic stimulation coupled with electromyography was applied before and immediately after the EA intervention. Resting motor threshold, motor evoked potential, short intracortical inhibition and intracortical facilitation were measured. RESULTS: EA increased corticospinal excitability of M1 compared to the control group only when administered with a frequency of 100 Hz at the sensory threshold (p < 0.05). There were no significant changes in the other measures. CONCLUSION: The results suggest that EA with an intensity level at the sensorial threshold and 100 Hz frequency increases the corticospinal excitability of M1. This effect may be associated with a decrease in the activity of inhibitory intracortical mechanisms. TRIAL REGISTRATION NUMBER: U1111-1173-1946 (Registro Brasileiro de Ensaios Clínicos; http://www.ensaiosclinicos.gov.br/).

Repeated neonatal needle-prick stimulation increases inflammatory mechanical hypersensitivity in adult rats.

BACKGROUND AND AIMS: Newborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period. METHODS: The animals were submitted to repetitive needle pricking from the second to the fifteenth postnatal day (PND 2-15). Maternal behavior and litter weight were evaluated during this period. Mechanical sensitivity to pain was assessed in offsprings during the adulthood by exposing them to inflammatory stimuli, including formalin test or the Freund's complete adjuvant (CFA) injection followed by the electronic von Frey test at 0, 3, 6 and 24 h later. RESULTS: Maternal behavior and litter weight were not altered by pinprick stimuli during PND 2-15. Additionally, pinprick stimulation reduced the paw withdrawal threshold in CFA-injected animals compared to control. In the formalin test, there was a difference between the genders. Female rats are statically more sensitive to formalin stimulation and showed an increased licking time in both the first and second phases and increased number of flinches in second phase. CONCLUSIONS: Experiencing early life repetitive pain exposure increased inflammatory pain sensitivity in adult offspring rats and female rats are more sensitive to chemical stimulation. IMPLICATIONS: Future investigations of the mechanisms involved in this effect may contribute to the improvement of the understanding of inflammatory pain sensitivity differences.

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.