Thermal Hyperesthesia Research Articles

Root coverage techniques for gum recession

INTRODUCTION: Gingival recession, also known as receding gums, is the exposure in the roots of the teeth caused by a loss of gum tissue and/or retraction of the gingival margin from the crown of the teeth. The aetiology of the condition is multifactorial but is commonly associated with underlying alveolar morphology, tooth brushing, mechanical trauma and periodontal disease PURPOSE: To highlight the importance of covering gingival recessions and the presentation of various surgical techniques of covering receding gums METHOD: A review of the literature of the last five years was performed, with keywords such as: gingival recession, surgical flaps, root coverage techniques. RESULTS: Main reasons of covering gingival recessions are thermal hyperesthesia and esthetics of the oral cavity. The root coverage can be achieved by using free gingival graft tissue from the hard palate of the patient or biomaterials such as bovine and synthetic material. CONCLUSIONS: The choice of the right technique for covering the gum recession plays an important role in the treatment plan. However, the surgeon should be experienced and make all the proper treatment planning choices for the esthetic result

Prognostic factors, symptom evolution, and quality of life of posttraumatic trigeminal neuropathy.

Neurosensory disturbances (NSDs) caused by injury to the trigeminal nerve can affect many aspects of daily life. However, factors affecting the persistence of NSDs in patients with posttraumatic trigeminal neuropathies (PTTNs) remain largely unknown. The identification of such risk factors will allow for the phenotyping of patients with PTTNs, which is crucial for improving treatment strategies. We therefore aimed to identify the prognostic factors of NSD persistence, pain intensity, and quality of life (QoL) in patients with PTTNs and to use these factors to create a prognostic prediction model. We first performed a bivariate analysis using retrospective longitudinal data from 384 patients with NSDs related to posttraumatic injury of the trigeminal nerve (mean follow-up time: 322 ± 302 weeks). Bivariate and multivariate analyses were performed. The multivariable prediction model to predict persistent NSDs was able to identify 76.9% of patients with persistent NSDs, with an excellent level of discrimination (area under the receiver operating characteristic curve: 0.84; sensitivity: 81.8%; specificity: 70.0%). Furthermore, neurosensory recovery was significantly associated with sex; injury caused by local anesthesia, extraction, third molar surgery, or endodontic treatment; and the presence of thermal hyperesthesia. Pain intensity and QoL analysis revealed several factors associated with higher pain levels and poorer QoL. Together, our findings may aid in predicting patient prognosis after dental, oral, and maxillofacial surgery and might lead to personalized treatment options and improved patient outcomes.

Population-based study of central post-stroke pain in Rimini district, Italy

Central post-stroke pain (CPSP) is still an underestimated complication of stroke, resulting in impaired quality of life and, in addition to the functional and cognitive consequences of stroke, the presence of CPSP may be associated with mood disorders, such as depression, anxiety, and sleep disturbances. This type of pain may also impair activities of daily living and further worsen quality of life, negatively influencing the rehabilitation process. The prevalence of CSPS in the literature is highly variable (1%–12%) according to different studies, and this variability could be influenced by selection criteria and the different ethnic populations being investigated. With this scenario in mind, we performed a population-based study to assess the prevalence of CPSP and its main features in a homogeneous health district (Rimini, Italy), including five hospitals for a total population of 329,970 inhabitants. From 2008 to 2010, we selected 1,494 post-stroke patients and were able to interview 660 patients, 66 (11%) of whom reported pain with related tactile and thermal hyperesthesia, accompanied by needle puncture, tingling, swelling, and pressure sensations. Patients reported motor impairment and disability, which influenced their working ability, rehabilitation, and social life. Despite this severe pain state, there was a high percentage of patients who did not receive adequate treatment for pain.

Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine from polymer fibers in the rat chronic constriction injury model

We aimed to evaluate the antihyperalgesic efficacy of a combination of hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a biodegradable cylindrical rod. In vivo studies were performed using a rat model of thermal hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10 mm length, 1 mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent to the constriction injury, immediately after nerve ligation. We evaluated the efficacy of two dose levels for each drug, alone or in combination, in attenuating thermal hyperesthesia over a period of 12 days according to a prevention protocol. Plasma levels of drugs released from the rods and also released in an in vitro simulation were evaluated. In vitro studies demonstrated that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5 mg) alone did not attenuate hyperalgesia. Their combination provided a significant increase in the paw withdrawal latency as compared to single agents or placebo. When the dose in each group was doubled, implanting four rods, significant attenuation of hyperalgesia was observed. Analyses of rods retrieved after termination of experiments (after 12 days) revealed 30% residual HM and 70% residual BP content. Prolonged delivery of HM and BP alone or in combination via locally applied PLGA rods may offer a feasible alternative to provide long-lasting analgesia.

Clonidine, but not morphine, delays the development of thermal hyperesthesia induced by sciatic nerve constriction injury in the rat.

It has been shown that the spinal facilitation induced by the injury discharge evoked by a nerve constriction injury is crucial in the development of thermal hyperesthesia. Both opioids and alpha 2 agonists have been reported to prevent the development of spinal facilitation evoked by the small afferent input to the spinal cord. Moreover, it has been reported that the thermal hyperesthesia induced by a nerve constriction injury is sympathetically maintained and that spinally administered alpha 2 agonists can modulate the sympathetic outflow from the spinal cord. The current study investigated the effect of spinally administered morphine and clonidine, an alpha 2 agonist, on the development of thermal hyperesthesia induced by nerve constriction injury in the rat. A model of thermal hyperesthesia induced by a constriction injury created by making four loose ligatures around the rat sciatic nerve was used to examine the development of thermal hyperesthesia. Morphine, clonidine, and idazoxan were administered intrathecally or intraperitoneally 20 min before (pretreatment study) or 20 min after (posttreatment study) the nerve injury. Pretreatment, but not posttreatment, with intrathecal clonidine significantly delayed the development of thermal hyperesthesia in a dose-dependent manner, and this delay in onset produced by clonidine was 3 days after the nerve injury. This effect of clonidine's was completely antagonized by the coadministration of idazoxan with clonidine. Intrathecal morphine had no effect on the development of thermal hyperesthesia in this study. Spinal alpha 2 receptors, but not opioid receptors, may play an important role in the development of thermal hyperesthesia induced by a nerve constriction injury. This suggested that the activation of spinal alpha 2 receptor may reduce the sympathetic outflow and this reduction of sympathetic outflow may be the key mechanism that delays the development of thermal hyperesthesia.

OP-1206, a Prostaglandin E1 Derivative, Attenuates the Thermal Hyperesthesia Induced by Constriction Injury to the Sciatic Nerve in the Rat

OP-1206, a Prostaglandin E1 Derivative, Attenuates the Thermal Hyperesthesia Induced by Constriction Injury to the Sciatic Nerve in the Rat

Role of Nitric Oxide in the Development of Thermal Hyperesthesia Induced by Sciatic Nerve Constriction Injury in the Rat

Nitric oxide (NO) has been shown to be involved in mediating nociceptive information transmission in the spinal cord. It is known that the N-methyl-D-aspartate receptor plays an important role in the development of the spinal facilitation evoked by a protracted small afferent input and that this effect is mediated at least in part by NO. Recently, it has been found that N-methyl-D-aspartate receptor-mediated spinal facilitation is crucial in the development of thermal hyperesthesia evoked by a nerve constriction injury. In the current study, we investigated the role of NO in the development of thermal hyperesthesia after a nerve constriction injury. The Bennett and Xie model (four loose chromic gut ligations around the rat sciatic nerve) was used to examine the development of thermal hyperesthesia. An NO synthase inhibitor (N omega-nitro-L-arginine or N omega-nitro-L-arginine methyl ester hydrochloride), rat hemoglobin, or L-arginine was administered intrathecally 10 min before the nerve injury (pretreatment study) or 15 min after the nerve injury (posttreatment study). Pretreatment but not posttreatment administration of NO synthase inhibitor significantly delayed the development of thermal hyperesthesia. The effect of NO synthase inhibitor was reversed by the coadministration of L-arginine but not by the coadministration of D-arginine. Pretreatment with rat hemoglobin also delayed the development of thermal hyperesthesia. L-Arginine itself had no effect on the development of thermal hyperesthesia. NO may play an important role in the development of N-methyl-D-aspartate receptor-mediated spinal facilitation after a nerve constriction injury.

OP-1206, a prostaglandin E1 derivative, attenuates the thermal hyperesthesia induced by constriction injury to the sciatic nerve in the rat.

Nerve ischemia induces wallerian degeneration and peripheral neuropathy, the nerve constriction injury induces thermal hyperesthesia. Nerve ischemia is one possible mechanism in the development of thermal hyperesthesia in the nerve constriction injury model. Prostaglandin E1 increases tissue blood flow. In the present study, the authors examine the role of nerve ischemia in the maintenance of the thermal hyperesthesia induced by nerve constriction injury by orally administering OP-1206, a prostaglandin E1 derivative. A nerve constriction injury model was created by making four loose ligations around the rat sciatic nerve, which induces thermal hyperesthesia in the ligated paw in 2-5 days. OP-1206, was administered six times (Day 7, one time; Day 8, two times; Day 9, two times; Day 10, one time). A single administration of OP-1206 had no effect on the thermal hyperesthesia. Six hours after the sixth-administration of OP-1206, the level of the thermal hyperesthesia was attenuated in a dose-dependent manner, and this effect lasted more than 1 day after the last drug administration. These data indicate that nerve ischemia plays an important role in maintaining the thermal hyperesthesia induced by nerve constriction injury in the rat.

OP-1206, a Prostaglandin E1 Derivative, Attenuates the Thermal Hyperesthesia Induced by Constriction Injury to the Sciatic Nerve in the Rat

OP-1206, a Prostaglandin E1 Derivative, Attenuates the Thermal Hyperesthesia Induced by Constriction Injury to the Sciatic Nerve in the Rat

Time-dependent Effect of Morphine and Time-independent Effect of MK-801, an NMDA Antagonist, on the Thermal Hyperesthesia Induced by Unilateral Constriction Injury to the Sciatic Nerve in the Rat

It is known that peripheral nerve injury induces time-dependent changes in dorsal horn function. The current study investigated the time dependency of the effects of intrathecal morphine and MK-801, an N-methyl-D-aspartate antagonist, on the thermal hyperesthesia evoked by unilateral constriction injury to the sciatic nerve in the rat. In rats with a unilateral constriction injury to the sciatic nerve, paw withdrawal latency against thermal stimulation for the injured paw was typically 3 s less than that for the uninjured paw during the first 5 weeks after the injury. Drugs were administered intrathecally 1 or 5 weeks after the nerve injury. Intrathecal morphine increased the paw withdrawal latencies of both the injured paw and the uninjured paw in an equally dose dependent manner in the 1-week study. In the 5-week study, morphine increased the paw withdrawal latency of the uninjured paw in a dose-dependent manner, but not that of the injured paw. Intrathecal MK-801 increased the paw withdrawal latency of the injured paw to the level of the uninjured paw in a dose-dependent manner in both the 1- and 5-week studies. These data indicate that (1) an N-methyl-D-aspartate receptor-mediated spinal facilitation may be the common mechanism maintaining the thermal hyperesthesia evoked by the constriction injury, and (2) the effects of intrathecal morphine on this thermal hyperesthesia are time-dependent.

Effects of FK224, a Novel Cyclopeptide NK1 and NK2 Antagonist, and CP-96,345, a Nonpeptide NK1 Antagonist, on Development and Maintenance of Thermal Hyperesthesia Evoked by Carrageenan Injection in the Rat Paw

The role of tachykinins, such as substance P and neurokinin A, in the development or maintenance of thermal hyperesthesia during inflammation is unclear. In the current study, the authors examined the role of NK1 and NK2 receptors on the thermal hyperesthesia evoked by injection of carrageenan into the rat paw using FK224, a cyclopeptide NK1 and NK2 antagonist, and CP-96,345, a nonpeptide NK1 antagonist. In rats injected with 2 mg carrageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carrageenan injection. In the pretreatment study, drugs were administered intravenously or intrathecally 10 min before the carrageenan injection. In the posttreatment study, drugs were administered intravenously or intrathecally 2 h after the carrageenan injection. In the pretreatment study, both intravenous CP-96,345 and intravenous FK224 blocked the development of thermal hyperesthesia and reduced paw edema in a dose-dependent manner 2 h after the carrageenan injection. The effect of CP-96,345 on thermal hyperesthesia was stereospecific, but that on paw edema was not. Posttreatment with intravenous CP-96,345 and intravenous FK224 failed to reduce the level of thermal hyperesthesia or paw edema, and intrathecal injections, either pre- or posttreatment, had no effect on thermal hyperesthesia or paw edema. These data indicate that: 1) spinal NK1 and NK2 receptors do not play an important role in development and maintenance of thermal hyperesthesia evoked by paw carrageenan, and 2) the peripheral NK1 receptor may play an important role in the development of thermal hyperesthesia, but not of paw edema.

Role of the Injury Disharge in the Development of Thermal Hyperesthesia after Sciatic Nerve Constriction Injury in the Rat

Usually, a barrage of impulses ("injury discharge") is evoked following sensory nerve damage. It has been suggested that injury discharge may produce the hyperexcitatory state in the spinal cord, and this hyperexcitability may cause neurogenic pain. In the present study, the authors examined the role of injury discharge in developing the hyperesthetic state following nerve constriction injury. A model of thermal hyperesthesia caused by a constriction injury created by making four loose ligations around the rat sciatic nerve was examined. To block the injury discharge, 0.5% bupivacaine was applied to the sciatic nerve before constriction injury. To block the hyperexcitatory state, (+)-MK-801, an N-methyl-D-aspartate antagonist, was administered intrathecally 15 min before the nerve lesion. Blocking injury discharge significantly delayed the development of hyperesthesia. Bupivacaine had no effect on the development of hyperesthesia when bupivacaine was applied to the sciatic nerve 15 min after the nerve constriction injury. Systemic bupivacaine had no effect on the development of thermal hyperesthesia. Intrathecal (+)-MK-801 also delayed the development of hyperesthesia when (+)-MK-801 was administered intrathecally 15 min before the nerve injury. When (+)-MK-801 was administered 15 min after the nerve injury, (+)-MK-801 had no effect on the development of hyperesthesia. These results suggest that injury discharge may induce facilitation of spinal dorsal horn neurons, and this spinal facilitation may play an important role in developing thermal hyperesthesia following sciatic nerve constriction injury.

Pathology of Experimental Compression Neuropathy Producing Hyperesthesia

An experimental neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve has recently been shown to produce pain-related behavior that follows a reproducible time course. In the present study, we assessed the degree of thermal hyperesthesia and examined the sciatic nerves by light and electron microscopy at different time points from 1 day to 12 weeks after surgery. Edema was the initial pathologic change seen in the neuropathy and was associated with early Wallerian degeneration on day 1. Injury to the connective tissue sheaths with interruption of the perineurial layer, infiltration of macrophages into the endoneurium, and proliferation of endothelial cells were observed during the first week. Endothelial cells hypertrophied and changed to a rhomboid shape with gaps between adjacent cells. Most large myelinated and many small myelinated fibers underwent Wallerian degeneration. Unmyelinated fiber numbers were reduced to one-third of the normal value from day 5 to day 14. Axonal sprouts were numerous after 1 week and grew into the segment distal to the ligatures by 4 weeks. Aberrant sprouts in minifascicles outside the perineurium were present from 4 weeks on. The original ligatures were rapidly surrounded by large amounts of fibrous tissue and mostly absorbed by 12 weeks; the initial fascicular compression caused by the ligatures was maintained by the fibrous tissue. We conclude that, whereas neuroma formation may contribute to the pain-related behavior in the later stages of this neuropathy, acute changes in the endoneurial microenvironment are important for its initial development.

Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists

This study evaluated the effects of spinally administered excitatory amino acid antagonists on the thermal hyperesthetic state induced by unilateral partial ligation of the sciatic nerve in the rat. The measured response was the latency to paw withdrawal of each hind paw after application of a focused heat lamp on the plantar surface of the paw through a glass plate upon which the animal stood. In this work, antagonists (MK801, dl-2-amino-5-phosphonovalerate, ketamine) of the N- methyl- d-aspartate receptor (NMDA), the glycine potentiation site at the NMDA receptor (5-chloro-indole-2-carboxylic acid) and non-NMDA receptor (kynurenic acid: g- d-glutamylaminomethyl sulphonate) were injected through chronically implanted lumbar intrathecal catheters in normal rats (no lesions) and in rats with unilateral constriction injury. In the normal rat study, NMDA and non-NMDA antagonists had little effect upon paw withdrawal latency at intrathecal doses which did not produce readily detectable motor weakness. In the hyperesthetic rat study, NMDA antagonists would temporarily eliminate the hyperesthetic state at doses below those which altered the response latency of the normal paw or which altered motor function. These results suggested that spinal NMDA receptors play an important role in the hyperesthetic state induced by peripheral nerve injury.

Spinal pharmacology of thermal hyperesthesia induced by incomplete ligation of sciatic nerve. I. Opioid and nonopioid receptors.

Mechanisms underlying the pain state in humans that follows incomplete injury to peripheral nerve are little understood. To gain better understanding of this phenomenon, this study evaluated the effects on the thermally evoked hind-paw withdrawal latency produced by the intrathecal administration of morphine, U-50 488H (U-50), (D-Pen2, D-Pen5)-enkephalin (DPDPE), ST-91, baclofen, muscimol, and 5'-N-ethylcarboxamide-adenosine (NECA) in normal rats and in rats with a hind paw rendered unilaterally hyperesthetic by the unilateral application of loose ligatures to the sciatic nerve. In the animals with one ligated nerve, the hind-paw latency for the ligated paw was typically 2-4 s less than that for the nonligated paw, at 7-11 days postoperatively. In normal rats prepared with chronic intrathecal catheters, dose-dependent increases in paw withdrawal latency were observed; the order of activity was: baclofen, ST-91, morphine, muscimol, DPDPE much greater than U50, NECA greater than or equal to 0. In the nonligated (nonhyperesthetic) paw of the lesioned animals, intrathecal agents also resulted in a dose-dependent increase in the paw withdrawal latency; the order of potency was: NECA, baclofen, morphine, ST-91, muscimol, DPDPE greater than U50 greater than or equal to 0. For both NECA and morphine, the median effective dose (ED50) values were significantly less in the nonhyperesthetic hind paw. For the hyperesthetic paw, the dose-response curves were parallel to those obtained concurrently in the nonhyperesthetic paw but were shifted significantly to the right by a factor of 3-5, with the rank order of activity in the hyperesthetic paw being baclofen, morphine, muscimol, DPDPE greater than ST-91, NECA, U50 greater than or equal to 0. These data indicate that 1) spinal receptor systems that alter thermal afferent processing in the normal animal are similarly active in the hyperesthetic paw of the lesioned animal; and 2) unexpectedly, despite similar predrug response latencies, certain receptor systems regulating the response in the nonhyperesthetic paw of the lesioned rat (morphine and NECA) show greater activity than in the nonlesioned rat.