A Preterm Rat Model for Pain Studies.

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain sensitivity. The primary objective of this protocol was to investigate the impact of neonatal pinprick stimuli on the pain threshold in the later stages of life using a preterm rat model. By establishing this model, we aim to advance the research on understanding and managing early postnatal pain associated with prematurity. The findings of this study indicate that while the baseline thresholds to mechanical stimuli remained unaffected, there was a notable increase in mechanical hypersensitivity following complete Freund's adjuvant (CFA) injection in adult rats. Interestingly, compared with male rats, female rats demonstrated heightened inflammatory hypersensitivity. Notably, maternal behavior, the weight of the litters, and the growth trajectory of the offspring remained unchanged by the stimulation. The manifestation of altered nociceptive responses in adulthood after neonatal painful stimuli could be indicative of changes in sensory processing and the functioning of glucocorticoid receptors. However, further research is needed to understand the underlying mechanisms involved and to develop interventions for the consequences of prematurity and neonatal pain in adults.

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.

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.

Laserpuntura na neuropatia periférica: efeitos na dor e qualidade de vida / Laserpuncture in peripheral neuropathy: effects on pain and quality of life

Introdução: A laserpuntura é utilizada para analgesia, embora os protocolos para aplicação na dor neuropática permaneçam contraditórios. Objetivo: Avaliar o efeito da laserpuntura na modulação da dor neuropática, impacto na qualidade de vida e processo inflamatório local. Material e métodos: Cinco pacientes com diagnóstico de lesão nervosa periférica e dor neuropática associada receberam aplicação do laser AlGaInP, 658 nm, 10 mW, 9 J/cm2, em acupontos especí­ficos, durante 15 sessões, 3 vezes na semana, por 50 minutos. A avaliação pré e pós-intervenção foi realizada pela Escala Visual Analógica, questionário para dor (McGill), questionário de qualidade de vida (SF-36), Índice de incapacidade de Oswestry e termografia. Resultados: Foi observada redução da média da pontuação na Escala Visual Analógica em 3 de 5 pacientes e redução da média de dor após 15 sessões. A avaliação pelo McGill mostrou redução nas dimensões afetivo, avaliativo e total. No questionário SF-36 foi observada melhora das dimensões Capacidade Funcional e Limitação por Aspectos Emocionais. No Índice de Oswestry observou-se redução da média da porcentagem e na termografia não houve diferença nos valores pré e pós-intervenção. Conclusão: Estes resultados sugerem eficácia da laserpuntura na redução da dor e melhora da qualidade de vida em pacientes com dor neuropática decorrente de lesão nervosa periférica. (AU)

Introduction: Laserpuncture is used for analgesia, although the protocols for use in neuropathic pain remain contradictory. Objective: To evaluate the effect of laserpuncture in modulating neuropathic pain, impact on quality of life and local inflammatory process. Methods: Five patients with peripheral nerve injury and neuropathic pain associated application received AlGaInP laser, 658 nm, 10 mW, 9 J/cm2 at specific acupoints for 15 sessions, 3 times a week for 50 minutes. The pre- and post-intervention were performed by Visual Analogue Scale, questionnaire for pain (McGill), quality of life questionnaire (SF-36), Oswestry disability index and thermography. Results: A significant reduction in Visual Analogue Scale score average was observed in 3 of 5 patients in addition to an overall reduction of average pain after 15 sessions. The evaluation by McGill showed reduction in affective, evaluative and overall dimensions. In the SF-36 questionnaire was observed an increase of the dimensions Functional Capacity and Emotional Aspects. In Oswestry Index a reduction was observed in the average percentage and in the thermography no difference was noticed in pre and post-intervention. Conclusion: These results suggest effectiveness of laser acupuncture in reducing pain and improving quality of life in patients with neuropathic pain due to peripheral nerve injury. (AU)

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.