Changes in properties of substantia gelatinosa neurons after surgical incision in the rat: in vivo patch-clamp analysis.
ABSTRACT Noxious information through A delta and C afferent fibers is transmitted to substantia gelatinosa, a process that plays an important role in plastic changes of nociceptive processing in pathophysiological conditions. In this study, changes in properties of substantia gelatinosa neurons and their sensitivity to systemic administration of lidocaine after surgical incision were investigated using the in vivo patch-clamp technique.
Under urethane anesthesia, in the current clamp mode, spontaneous activities and responses of substantia gelatinosa neurons to nonnoxious air-puff stimuli and noxious pinch stimuli were recorded before and after 1-cm-long incisions had been made in hairy skin of the hindquarters of rats. Systemic administration of lidocaine (2 mg/kg) was applied at 30 min after the incision.
Stable recordings for 30 min or more after the incision were obtained from 18 substantia gelatinosa neurons that were classified as multireceptive (n = 8), nociceptive (n = 5), and subthreshold (n = 5) neurons. Action potential firing disappeared immediately after completion of the wound closure in most multireceptive and nociceptive neurons, and sustained spontaneous action potential firing was observed in 23% of these substantia gelatinosa neurons. Responsiveness of these substantia gelatinosa neurons, but not that of subthreshold neurons, increased after the incision. Systemic administration of lidocaine suppressed spontaneous firings of action potentials of the substantia gelatinosa neurons and reversed the increased responsiveness of the neurons.
The results suggest that (1) changes in properties of substantia gelatinosa neurons after incision vary depending on the classification of substantia gelatinosa neurons and (2) systemic administration of lidocaine can reverse increased responsiveness of substantia gelatinosa neurons after incision injury.
- [show abstract] [hide abstract]
ABSTRACT: The superficial dorsal horn, particularly substantia gelatinosa (SG) in the spinal cord, receives inputs from small-diameter primary afferents that predominantly convey noxious sensation. This sensory information via the high-threshold Adelta and C afferents is modified and integrated in SG, and consequently regulates the outputs of projection neurons located in lamina I and laminae IV-V. Recent studies using slice and in vivo patch-clamp recordings indicate that the sensory inputs to SG are functionally reorganized during post-natal development. Even in the mature state, the synaptic connectivity and receptor expression in SG can be altered easily following peripheral tissue damage. In addition, the descending pain inhibitory system to SG is also modified under certain pathological conditions. Considering that the pain system is phylogenetically primitive, it is, therefore, not surprising that the system easily exhibits a plastic change in response to inflammation or nerve damage. Because such plastic changes in the neuronal circuit or receptor expression in SG are now generally accepted to be one of the explanations for the induction of pathological pain, SG is thought to be a primary therapeutic target for chronic pain. We review here recent results demonstrating plastic changes in SG under pathological conditions.Neuroscience Research 05/2004; 48(4):361-8. · 2.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: In this study, we developed a rat model of incisional pain. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the hindpaw in halothane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at different areas around the wound before surgery and for the next 6 days. A cumulative pain score based on the weight bearing behavior of the animals was also utilized. The results of tests for withdrawal responses and scores based on weight bearing suggest that a surgical incision of the rat foot causes a reliable and quantifiable mechanical hyperalgesia lasting for several days after surgery. An incision that only included skin and fascia but not muscle in the foot caused less severe hyperalgesia during the initial postoperative period. Distinct areas around the wound had different withdrawal thresholds during the study period. Even remote sites as much as 10 mm from the wound showed persistent mechanical hyperalgesia. Selective denervations of the rat hindpaw prior to foot incision revealed both the sural and tibial nerves were responsible for transmitting input from the incision that produces hyperalgesia. This model should allow us to understand mechanisms of sensitization caused by surgery and investigate new therapies for postoperative pain in humans.Pain 04/1996; 64(3):493-501. · 5.64 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Hypersensitivity after tissue injury is an expression of neuronal plasticity in the central nervous system. This has been explored most extensively using in vitro preparations and animal models of inflammatory pain and chemical irritation. For pain after surgery, a similar process has been proposed. In the present study, we examined dorsal horn neuron (DHN) sensitization using the plantar incision model for post-operative pain. In behavioral experiments, the effect of a local anesthetic injection (or saline vehicle) 15 min before plantar incision on pain behaviors several days after incision was studied. Bupivacaine injection before incision prevented pain behaviors until 4 h afterwards; injection after incision produced the same effect. One day after incision, pain behaviors were not different between rats injected with saline or bupivacaine. In neurophysiologic experiments, however, bupivacaine injection blocked activation of DHNs during incision. One hour after incision, expansion of receptive fields (RFs) to pinch and increased background activity occurred in 14 of 16 neurons in the saline group but only in two of 22 neurons in the bupivacaine group. The difference was not due to a systemic effect of bupivacaine. Ten sensitized neurons were studied using the injection of bupivacaine 90 min after incision. Increased background activity (n=7) and expanded RFs (n=7) were reversed by bupivacaine. Sensitization was re-established in seven of eight neurons 2 h after injection as the local anesthetic dissipated. These results indicate that activation of DHNs during plantar incision and sensitization 1 h later are not necessary for subsequent pain behaviors. Because sensitization was reversed 90 min after plantar incision and then re-established as the local anesthetic effect diminished, enhanced responsiveness of DHN requires ongoing afferent input during the first day after incision.Pain 06/2002; 97(1-2):151-61. · 5.64 Impact Factor