| Hypothyroidism-induced pain is one of the most common complications in patients suffering from hypothyroidism.Hypothyroidism induced pain is often manifested as complex pathological pain symptoms including headache,chest pain,and muscle pain,during which muscle pain has been regarded as the most common disease seriously influencing the quality of life of patients.Currently,various studies have proposed that the imbalanced thyroid hormone supply might be the main reason resulting pain symptoms,during which the direct evidence and the detailed pathogenesis is still not clear.In this study,we established an animal model of hypothyroidism in rats by thyroidectomy of all thyroid tissues,and observed the thyroid hormone levels and nociceptive behavioral activities in hypothyroid rats at 7,14,21 and 28 days after the thyroidectomy.Our previous series of studies have proposed a new concept of 43℃ heating-needle therapy,which may cause no obvious or less pain feeling,in treating pathological pain.Based on these,effects of 43℃ heating-needle treatment in treating hypothyroidism-induced pain during the period of 7,14,21 and 28 days after the thyroidectomy were investigated in the current study.Furthermore,mechanisms of thalamic ventromedial nucleus in effects of heating-needle treatment in control of hypothyroidism pain were explored.It provides a theoretical basis for the treatment of pain symptoms in patients with clinical hypothyroidism.Purposes:1.To explore the alterations in the endogenous modulatory effects of nociception at 7,14,21 and 28 days after the hypothyroid thyroidectomy.2.To explore the possible effects of intramuscular treatment with heating-needle at temperature of 43℃ on the endogenous modulation of hypothyroidism nociception at 7,14,21 and 28 days after thyroidectomy.3.To explore the possible efficacy of intramuscular treatment with heating-needle at temperature of 43℃ on hypothyroidism induced pathological pain at 7,14,21 and 28 days after thyroidectomy.4.To explore the modulation mechanisms mediated by the VM nucleus of the thalamus in the treatment of hypothyroid pain by heating-needle treatment at temperature of 43℃.Methods:1.Model establishment: the hypothyroidism model was established by removing bilateral thyroid tissues of female rats.The hypothyroid rats were tested for indexes at before the modeling and 7-28 days after the modeling,including basal metabolic indexes such as body temperature,body weight,heart rate,temperature preference.Other basal metabolic indexes,such as paw withdrawal thermal latency and paw withdrawal mechanical threshold of bilateral hind limbs,were recorded to evaluate nociception.2.Muscle pain model establishment: 0.2 ml of 5.8% hypertonic saline was given to the middle of the left gastrocnemius muscle of rats at 7 days after surgery,and the changes of paw withdrawal mechanical threshold and paw withdrawal thermal latency were observed in rats within 4 hours after the injection of hypertonic saline,respectively.3.Heating-needle treatment: the left gastrocnemius muscle of rats was treated with heating-needle treatment at temperature of 43℃ for 45 minutes at 7,14,21 and 28 days after surgery,and paw withdrawal mechanical threshold and paw withdrawal thermal latency were observed in rats within 4 hours and 1-7 days after treatment.Experimental results:1.Before the thyroidectomy,heart rate,body weight,body temperature,paw withdrawal mechanical threshold,and paw withdrawal thermal latency in each group of rats,there was no statistically significant difference between the data of each group(P > 0.05).In the thyroidectomized rats,a significant decrease in serum T4 concentration was observed at 7 days postoperatively and continued until 28 days postoperatively(P < 0.05).A trend of decrease in serum T3 concentration was observed at 14 days postoperatively and continued until 28 days postoperatively,with statistically significant differences(P < 0.05).The above indicators suggest that rats with light hypothyroidism at 7-14 days after thyroidectomy,and transformed to heavy hypothyroidism at 21-18 days.At the same time,the hypothyroid rats showed mechanical hyperalgesia that lasted for 14-28 days,which was statistically significantly different(P < 0.05).The paw withdrawal thermal latency in hypothyroid rats did not change significantly in all phases(P > 0.05).2.7 days after thyroidectomy: There was no significant change in paw withdrawal mechanical threshold and no significant change in paw withdrawal thermal latency in rats.When 0.2ml of 0.9% saline and 5.8% hypertonic saline were injected into the left gastrocnemius muscle,both experimental and control rats showed mechanical hyperalgesia,and the mechanical hyperalgesia was more severe in the experimental rats,with statistically significant differences(P < 0.05).There was no significant change in paw withdrawal thermal latency and paw withdrawal mechanical threshold in rats within 4 hours and 1-7 days after 45 minutes of treatment with single heating-needle treatment at temperature of 43℃.After double heating-needle treatment at temperature of 43℃ for 45 minutes,there was no significant change in paw withdrawal thermal latency in control rats within 4 hours and 1-7 days,and the rats in the experimental group showed a decrease in bilateral heat-evoked paw withdrawal latencies,which lasted 5 days after treatment,and there was a statistically significant difference compared with the control group(P < 0.05).There was no significant effect of double heating-needle treatment on paw withdrawal mechanical threshold in rats.3.14 days after thyroidectomy: rats showed a significant decrease in paw withdrawal mechanical threshold,i.e.,mechanical nociceptive hypersensitivity,and no significant change in paw withdrawal thermal latency.After single heating-needle treatment for 45 minutes,there was no significant change in paw withdrawal thermal latency and paw withdrawal mechanical threshold in rats within 4 hours and 1-7 days,and there was no significant difference compared with the control group(P > 0.05).After double heating-needle treatment for 45 minutes,there was no significant change in the paw withdrawal thermal latency in rats in the control group within 4 hours and 1-7 days,while rats in the experimental group showed a decrease in bilateral heat-evoked paw withdrawal latencies,which lasted 3 days after treatment,and there was a statistically significant difference compared with the control group(P < 0.05).There was no significant effect on the paw withdrawal mechanical threshold in rats.4.21 days after thyroidectomy: the paw withdrawal mechanical threshold in rats decreased significantly,i.e.,mechanical nociceptive hypersensitivity occurred,and there was no significant change in the paw withdrawal thermal latency.There was no significant change in paw withdrawal thermal latency and paw withdrawal mechanical threshold in rats within 4 hours and 1-7 days after 45 minutes with single and double heating-needle treatment,and there was no significant difference compared with the control group(P > 0.05).After treatment with quadruple heating-needle,there was no significant change in paw withdrawal thermal latency in rats in the control group within 4 hours and 1-7 days,while rats in the experimental group showed reduced bilateral heat-evoked paw withdrawal latencies,which lasted 5 days after treatment,and rats in the postoperative 28 days lasted 4 days after treatment,and the differences were all statistically significant compared with the control group(P< 0.05).There was no significant effect on paw withdrawal mechanical threshold in rats.5.28 days after thyroidectomy: rats showed a significant decrease in paw withdrawal mechanical threshold,i.e.mechanical nociceptive hypersensitivity,and no significant change in paw withdrawal thermal latency.After single and double heating-needle treatment,there was no significant change in paw withdrawal mechanical threshold and paw withdrawal thermal latency in rats within 4 hours and 1-7 days,and there was no significant difference compared with the control group(P > 0.05).After quadruple heating-needle treatment,there was no significant change in paw withdrawal thermal latency in rats in the control group within 4 hours and 1-7 days,while the rats in the experimental group showed a decrease in bilateral heat-evoked paw withdrawal latencies,which lasted 4 days after treatment,and the differences were statistically significant compared with the control group(P < 0.05).There was no significant effect on paw withdrawal mechanical threshold in rats.6.Microinjection of P2X3 receptor antagonists into the VM nucleus of the thalamus reversed the phenomenon of reduced heat-evoked paw withdrawal latencies induced by double heating-needle treatment at temperature of 43℃ in hypothyroid rats,and showed a dose-dependent effect,i.e.,the reversal effect was gradually evident with increasing injection dose(P < 0.05).Conclusions:1.The endogenous facilitation of pain in hypothermic rats is significantly enhanced,after the 14 days bilateral thyroidectomy.2.Multiple heating-needle treatment at temperature of 43℃ significantly enhance the endogenous inhibition of pain in rats of hypothyroidism.3.The P2X3 receptors in the ventralmedial nucleus of the thalamus are involved in the enhanced endogenous inhibition induced by double heating-needles treatment at temperature of 43℃. |
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