Associating high intensity and modulated frequency of TENS delays analgesic tolerance in rats.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic resource extensively used in painful conditions. However, preclinical studies suggest that the prolonged use of TENS results in the development of tolerance to its analgesic effect. The present study investigated the analgesic effect and development of tolerance to TENS with four different stimulation protocols. METHODS: Male Wistar rats induced with joint inflammation were divided into four groups: sensory intensity, low motor intensity, high motor intensity and sham groups. TENS was applied daily for 20 min with alternating frequency between 4 and 100 Hz until tolerance development was evidenced. Mechanical hyperalgesia was measured before and after each TENS daily application. RESULTS: After TENS, tolerance was evidenced There was a significant reduction in the mechanical withdrawal threshold in all groups 24 h after induction of inflammation (p < 0.01). We observed a loss of analgesic efficacy of TENS around the 12th, 19th and 19th days in the groups treated with sensory intensity, low motor intensity and high motor intensity, respectively (p < 0.02) when analysed using paired measurements and compared with the control. CONCLUSIONS: The association between frequency variation and intensity at motor level promotes a delay in the development of analgesic tolerance to TENS, optimizing and extending its therapeutic effectiveness.

Experimental hypothyroidism during pregnancy affects nociception and locomotor performance of offspring in rats.

BACKGROUND: Thyroid hormones (THs) play a crucial role in the development of several organic systems. An adequate support of maternal THs may be required to ensure a normal nociceptive function of offspring into adulthood. We investigated the impact of experimental gestational hypothyroidism (EGH) on nociceptive threshold and motor performance in the offspring at different post-natal days (PND) in both male and female rats. METHODS: EGH was induced by the administration of 0.02% methimazole (MMI) in the drinking water from the ninth day of gestation until birth. The offspring from MMI-treated dams (OMTDs) or from water-treated dams (OWTDs) were assessed for thermal and mechanical nociception using the tail-flick test and von Frey filaments, respectively. Both rota-rod and grip strength were used to assess motor function. RESULTS: OMTD had reduced thermal (p<0.05) but not mechanical threshold at all studied ages (60 and 120 PND). Sixty-day-old OMTD presented reduced latency to the tail-flick test (p=0.01). Grip strength in 120-day-old OMTD was reduced (p<0.01). However, only male OMTD presented a lower locomotor performance on the rota-rod test when analysed on the 60th PND (p<0.01). CONCLUSIONS: EGH promotes hypersensitivity to noxious thermal but not mechanical stimulus. Moreover, motor force is similarly reduced in male and female OMTDs, whereas motor performance is reduced only in mature male OMTD, suggesting the presence of a protective factor in females.

Transcutaneous electrical nerve stimulation at both high and low frequencies activates ventrolateral periaqueductal grey to decrease mechanical hyperalgesia in arthritic rats.

Transcutaneous electric nerve stimulation (TENS) is widely used for the treatment of pain. TENS produces an opioid-mediated antinociception that utilizes the rostroventromedial medulla (RVM). Similarly, antinociception evoked from the periaqueductal grey (PAG) is opioid-mediated and includes a relay in the RVM. Therefore, we investigated whether the ventrolateral or dorsolateral PAG mediates antinociception produced by TENS in rats. Paw and knee joint mechanical withdrawal thresholds were assessed before and after knee joint inflammation (3% kaolin/carrageenan), and after TENS stimulation (active or sham). Cobalt chloride (CoCl(2); 5 mM) or vehicle was microinjected into the ventrolateral periaqueductal grey (vlPAG) or dorsolateral periaqueductal grey (dlPAG) prior to treatment with TENS. Either high (100 Hz) or low (4 Hz) frequency TENS was then applied to the inflamed knee for 20 min. Active TENS significantly increased withdrawal thresholds of the paw and knee joint in the group microinjected with vehicle when compared to thresholds prior to TENS (P<0.001) or to sham TENS (P<0.001). The increases in withdrawal thresholds normally observed after TENS were prevented by microinjection of CoCl(2) into the vlPAG, but not the dlPAG prior to TENS and were significantly lower than controls treated with TENS (P<0.001). In a separate group of animals, microinjection of CoCl(2) into the vlPAG temporarily reversed the decreased mechanical withdrawal threshold suggesting a role for the vlPAG in the facilitation of joint pain. No significant difference was observed for dlPAG. We hypothesize that the effects of TENS are mediated through the vlPAG that sends projections through the RVM to the spinal cord to produce an opioid-mediated analgesia.