Effect of plantar local anesthetic injection on dorsal horn neuron activity and pain behaviors caused by incision

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.

Monoamine-Dependent, Opioid-Independent Antihypersensitivity Effects of Intrathecally Administered Milnacipran, a Serotonin Noradrenaline Reuptake Inhibitor, in a Postoperative Pain Model in Rats

“…In contrast, intrathecal administration of non-NMDA receptor antagonists or neurokinin-1 receptor antagonists (Yamamoto and Sakashita, 1999) are effective. Dorsal horn neurons are sensitized after incision, but this sensitization is completely reversed by intraplantar injection of a local anesthetic (Pogatzki et al, 2002b). Furthermore, although descending facilitation from the rostral ventromedial medulla contributes to behavioral hypersensitivity of diverse animal models of inflammatory and neuropathic pain (Porreca et al, 2002), this mechanism is not involved in the hypersensitivity after incision (Pogatzki et al, 2002a).…”

Somatic paravertebral block decreases opioid requirements in children undergoing appendectomy

“…Intranasal ketorolac has recently become available and has been demonstrated to decrease morphine requirements and to reduce overall pain levels when used postoperatively. 16 Also, gabapentin-type drugs, including pregabalin, 17 as well as local anesthetic injection at the surgical site 18 have been demonstrated to be effective in multimodal analgesia. It is likely that the combination of drugs used in our study provided similar combined analgesic effects to both study groups.…”

Modality-specific Somatosensory Changes in a Human Surrogate Model of Postoperative Pain

“…4 -7 Data from well-established animal models of incisional pain have shown that peripheral sensitization of nociceptive afferents after skin incision contributes to ongoing pain 8,9 and increased sensitivity restricted to the site of incision (primary hyperalgesia). 10 Amplified activation of nociceptive afferents triggers plastic changes at synapses of central nociceptive neurons in the spinal cord (central sensitization), 11 leading to an increased sensitivity in an area remote from the incision (secondary hyperalgesia). 10,12,13 Generally, enhanced synaptic strength has been suggested to depend on long-term potentiation of synaptic transmission in the spinal cord.…”

“…11 The preclinical data suggest that the interaction of peripheral and central pain-enhancing mechanisms may be crucial for the experience of postoperative pain.…”