Responses of Primary Afferent Fibers to Acupuncture-Like Peripheral Stimulation at Different Frequencies: Characterization by Single-Unit Recording in Rats / 神经科学通报·英文版

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.

Mechanical Hyperalgesia Induced by Blocking Calcium-activated Potassium Channels on Capsaicin-sensitive Afferent Fiber

Small and large conductance Ca2+-activated K+ (SKCa and BKCa) channels are implicated in the modulation of neuronal excitability. We investigated how changes in peripheral KCa channel activity affect mechanical sensitivity as well as the afferent fiber type responsible for KCa channel-induced mechanical sensitivity. Blockade of SKCa and BKCa channels induced a sustained decrease of mechanical threshold which was significantly attenuated by topical application of capsaicin onto afferent fiber and intraplantar injection of 1-ethyl-2-benzimidazolinone. NS1619 selectively attenuated the decrease of mechanical threshold induced by charybdotoxin, but not by apamin. Spontaneous flinching and paw thickness were not significantly different after KCa channel blockade. These results suggest that mechanical sensitivity can be modulated by KCa channels on capsaicin-sensitive afferent fibers.

Comparative Study on the Nociceptive Responses Induced by Whole Bee Venom and Melittin

The present study was undertaken to confirm whether melittin, a major constituent of whole bee venom (WBV), had the ability to produce the same nociceptive responses as those induced by WBV. In the behavioral experiment, changes in mechanical threshold, flinching behaviors and paw thickness (edema) were measured after intraplantar (i.pl.) injection of WBV (0.1 mg & 0.3 mg/paw) and melittin (0.05 mg & 0.15 mg/paw), and intrathecal (i.t.) injection of melittin (6microgram). Also studied were the effects of i.p. (2 mg & 4 mg/kg), i.t. (0.2microgram & 0.4microgram) or i.pl. (0.3 mg) administration of morphine on melittin- induced pain responses. I.pl. injection of melittin at half the dosage of WBV strongly reduced mechanical threshold, and increased flinchings and paw thickness to a similar extent as those induced by WBV. Melittin- and WBV-induced flinchings and changes in mechanical threshold were dose- dependent and had a rapid onset. Paw thickness increased maximally about 1 hr after melittin and WBV treatment. Time-courses of nociceptive responses induced by melittin and WBV were very similar. Melittin-induced decreases in mechanical threshold and flinchings were suppressed by i.p., i.t. or i.pl. injection of morphine. I.t. administration of melittin (6microgram) reduced mechanical threshold of peripheral receptive field and induced flinching behaviors, but did not cause any increase in paw thickness. In the electrophysiological study, i.pl. injection of melittin increased discharge rates of dorsal horn neurons only with C fiber inputs from the peripheral receptive field, which were almost completely blocked by topical application of lidocaine to the sciatic nerve. These findings suggest that pain behaviors induced by WBV are mediated by melittin-induced activation of C afferent fiber, that the melittin- induced pain model is a very useful model for the study of pain, and that melittin-induced nociceptive responses are sensitive to the widely used analgesics, morphine.

DEVELOPMENTAL ORGANIZATION OF PRIMARY AFFERENT FIBERS IN THE DORSAL HORN OF THE MOUSE LUMBAR SPINAL CORD / 神经解剖学杂志

The present study was designed to examine the morphological pattern of primary afferent projections into the spinal dorsal horn by labeling the lumbar dorsal root ganglia with carbocyanine fluorescent dye DiI in mouse embryos and neonatal pups aged embryonic day 12 to postnatal day 3 (E12-P3). Primary afferent fibers projected into dorsal funiculus at E13, but did not penetrated into gray matter of dorsal horn until E15. The afferent projections became dense and entered the spinal gray matter more deeply at E16 and E17. By E18 the intensity of primary afferent in the deep part of the dorsal horn increased and their branching patterns became more complicated. Some of these primary fibers were also observed to ramify extensively in the superficial laminae. The projection pattern of primary afferent remained unchanged after birth, but the intensity of afferent terminals increased in the superficial laminae. In addition, afferent fiber collaterals that projected into the contralateral dorsal horn were also observed. They were first examined at E16 and mainly originated from the medial and deep part of the dorsal horn. Around birth, the contralateral projections were also found to originate from the lateral part of dorsal horn. Our results indicate that laminar organization of primary afferents in the spinal dorsal horn is established during the late embryonic and early postnatal stages.This organization then undergoes further refinement to match the pattern seen in the adult.

EFFECTS OF MORPHINE ON THE TERMINAL OF AFFERENT FIBER OF INJURED SCIATIC NERVE IN SPINAL LAMINA Ⅱ OF RAT——A HISTOCHEMICAL STUDY OF THE FLUORIDE-RESISTANT ACID PHOSPHATASE (FRAP) / 解剖学报

Objective To explore the effects of morphine on the terminal of primary afferent fiber distributing in spinal lamina Ⅱ after the sciatic nerve crush. Methods The positive reactive areas of fluoride-resistant acid phosphatase(FRAP) at spinal lamina Ⅱ were measured by the FRAP histochemistry and microcomputer image analysis techniques, after sciatic nerve was injured 15 days and 30 days both in morphine and control groups of rats. Results The positive reactive areas of FRAP at spinal lamina Ⅱ were depleted on different degree in two groups of rat after sciatic nerve was injured. The positive reactive areas of FRAP were greater 40% on injured sciatic nerve in 30 days than in 15 days in control group. In morphine group, the positive reactive areas of FRAP were larger 22% on injured sciatic nerve in 30 days than in 15 days; simulaneously also were bigger 19% than on injured sciatic nerve 30 days of control group.Conclusion The positive reactive areas of FRAP at spinal lamina Ⅱ show recovering enlargement as the surviving time lengthens in both groups of rats injured sciatic nerve.Morphine may enhance the positive reactive area of FRAP at spinal lamina Ⅱ in rat of sciatic nerve crush.