| Neuropathic pain(NP)is defined as pain initiated or caused by a lesion or dysfunction in the somatosensory system.Due to significant morbidity,it presents a challenging public health problem especially for elder patients 3.Although there are many studies investigating the mechanism of the development and maintenance of NP,the specific details remain unknown.As a result,NP remains a clinically refractory pain which needs further researches.Chemokine C-C motif ligand 2(CCL2,also named monocyte chemoattractant protein 1)is a member of the chemokines family and can play a key role in the chemotaxis of monocytes to sites of trauma,infection,toxin exposure,and ischemia.CCL2 has low expression under normal conditions but is immediately upregulated in early stage of nerve injury.The expression of CCL2 and its receptor(CC chemokine family receptor 2,CCR2)are increased in dorsal horn of spinal cord in NP model rat.Notably,intrathecal injection of CCL2 produces an evident nociceptive pain behavior in non-inflamed rats.Moreover,intrathecal preemptive administration of CCR2 antagonist substantially attenuates both nerve injury-induced pain behavior and the release of inflammatory cytokines.Taken together,these results imply that CCL2 and CCR2 are critical players in the development and maintenance of NP evoked by nerve injury.Pulsed radiofrequency(PRF)is a novel therapeutic strategy that has recently been used by pain practitioners as a non-or minimally neurodestructive technique.It is delivered in a pulse of 20 milliseconds(ms)followed by a silent period of 480 ms to avoid radiofrequency heat lesions.Some studies have shown that PRF is typically believed to modulate the pain pathology though reducing inflammatory factors,inhibiting protein kinase,adjusting calcium channels,and so on.However,whether PRF reduces NP by modulating the expression of CCL2 has not been reported.In this study,it is to explore whether PRF can alleviate neuropathic pain by regulating CCL2 expression in the spinal cord.Objective: This study aims to explore whether PRF can alleviate neuropathic pain by regulating CCL2 expression and its mechanism through a series of experiments.Methods: Part 1: 96 patients with acute / subacute trigeminal herpes zoster neuralgia were selected and divided into two groups: PRF group and sham group.Patients in PRF group was given PRF therapy on the semilunar ganglion,while patients in sham group was given needle acupuncture on the semilunar ganglion but without any pulse radiofrequency energy: 1.The pain scores were recorded before treatment and on 3 days,7 days,14 days,1 month,3 months and 6 months after treatments 2.The scores of qualities of life were also recorded before treatment and on 7 days,1 month,3 months and 6 months after treatment.Part 2: The animal model of neuropathic pain was established by sciatic nerve injury(SNI),and the expression of CCL2/NF-?B in spinal cord of SNI rats was verified.1.To establish SNI rat model,20 healthy S-D rats were randomly divided into six groups(n = 4): sham group,1 day group,3 days group,7 days group and 14 days group.2.Paw withdrawal mechanical threshold(PWMT)was assessed with the up-down method described previously using a set of von Frey hairs in in early stage after SNI injury.3.The expression of CCL2 and NF-?B was detected by western blot for injured L4-6 spinal cord,and the changes rule with time were also observed.4.The activities of microglia labeled by CCL2 in the spinal cord were detected by immunofluorescence method,and the changes rule with time were also observed.Part 3(1): To observe the improvement of pain behavior and the expression of CCL2 / NF-?B in spinal cord of in early stage of SNI injury rats treated with pulsed radiofrequency.1..16 SNI rats were randomly divided into two groups(n = 8): SNI group and pulse radiofrequency group.In the SNI group,the radiofrequency needle was punctured to the outer foramen of the intervertebral foramen without any pulse radiofrequency therapy;in the pulse radiofrequency group,the radiofrequency needle was punctured to the outer foramen of the intervertebral foramen and standard pulse radiofrequency therapy was given at 42 ?,2Hz for 120 seconds.2.Paw withdrawal mechanical threshold(PWMT)was assessed with the up-down method described previously using a set of von Frey hairs in in early stage after SNI injury in two groups.3.The expression of CCL2 and NF-?B was detected by western blot for injured L4-6 spinal cord,and the changes rule with time were also observed in two groups.4.The activities of microglia labeled by CCL2 in the spinal cord were detected by immunofluorescence method,and the changes rule with time were also observed in two groups.Part 3(2): To compare the improvement of pain behavior in SNI rats treated with different modes pulsed radiofrequency and to verify the changes expression of CCL2/NF-?B in spinal cord.1.16 SNI rats were randomly divided into two groups(n = 8): standard PRF group and long-term high-voltage PRF group.2.Paw withdrawal mechanical threshold(PWMT)was assessed with the up-down method described previously using a set of von Frey hairs in in early stage after SNI injury in two groups.3.The expression of CCL2 and NF-?B was detected by western blot for injured L4-6 spinal cord,and the changes rule with time were also observed in two groups.4.The activities of microglia labeled by CCL2 in the spinal cord were detected by immunofluorescence method,and the changes rule with time were also observed in two groups.Results: Part 1: The changes of pain scores in patients with acute / subacute trigeminal herpes zoster after PRF therapy.1.The postprocedure VAS scores in the PRF group were significantly lower than those in the sham group at different time points after treatment(P < 0.01).2.The SF-36 scores,which included physical functioning,physical role,bodily pain,general health perceptions,vitality,social function,emotional role,and the mental health index,were significantly improved at the sixth month after treatment in the PRF group compared to the sham group(P < 0.01).Part 2: The animal model of neuropathic pain was established by sciatic nerve injury(SNI),and the expression of CCL2/NF-?B in spinal cord of SNI rats was verified.1.There were significant declines of PWMT on different days after nerve injury in SNI group compared to sham group(P < 0.001).2.In the early stage of SNI,the expression of CCL2/ NF-?B were immediately increased on 1,3,7 and 10 days.3.In the early stage of SNI,the activities of microglia labeled by CCL2 in the spinal cord were immediately increased on 1,3,7 and 10 days.Part 3(1): to observe the improvement of pain behavior and the expression of CCL2 / NF-?B in spinal cord of in early stage of SNI injury rats treated with PRF treatment.1.There were significant improvements of PWMT on different days after nerve injury in PRF group compared to SNI group(P < 0.01).2.In the early stage after sciatic nerve section injury,there were less expressions of CCL2/NF-?B in PRF group compared to SNI group(P < 0.05).3.In the early stage after sciatic nerve section injury,there were less activities of microglia labeled by CCL2 in the spinal cord in PRF group compared to SNI group.Part 3(2): to compare the improvement of pain behavior in SNI rats treated with different modes PRF and to verify the changes expression of CCL2/NF-?B in spinal cord.1.There were significant improvements of PWMT on different days after nerve injury in long-term high-voltage PRF group compared to standard PRF group(P < 0.05).2.In the early stage after sciatic nerve section injury,there were less expressions of CCL2/NF-?B in long-term high-voltage PRF group compared to standard PRF group(P < 0.05).3.In the early stage after sciatic nerve section injury,there were less activities of microglia labeled by CCL2 in the spinal cord in long-term high-voltage PRF group compared to standard PRF group.Conclusion: 1.PRF on the Gasserian ganglion can obviously relieve the pain of acute/ subacute zoster-related trigeminal neuralgia and improve the quality of life.2.At the early stage of SNI,there were significant declines of PWMT on different days.The expressions of CCL2/NF-?B and the activities of microglia labeled by CCL2 were significant increased.3.PRF therapy can significantly alleviate the mechanical hyperalgesia of rats by reducing the expression of CCL2/NF-?B and the activities of microglia labeled by CCL2 in spinal cord.Compared to standard PRF therapy,long-term high-voltage PRF can get better analgesic effect though less expression of CCL2/NF-?B and the activities of microglia labeled by CCL2 in spinal cord. |
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