1. Psychophysical studies were made, in humans, of the sensory characteristics and underlying mechanisms hyperalgesia (often termed “secondary hyperalgesia”) that occurs uninjured skin surrounding a local cutaneous injury. The was characterized by lowered pain thresholds enhanced magnitude to normally painful stimuli. “injury” produced single intradermal injection 10 microliters 100 micrograms capsaicin, algesic substance hot chili peppers. 2. On capsaicin into volar forearm, subjects...

Substance P is released in the spinal cord response to painful stimuli, but its role nociceptive signaling remains unclear. When a conjugate of substance and ribosome-inactivating protein saporin was infused into cord, it internalized cytotoxic lamina I neurons that express receptor. This treatment left responses mild noxious stimuli unchanged, markedly attenuated highly mechanical thermal hyperalgesia. Thus, receptor play pivotal transmission maintenance

1. The contribution of activity in spinothalamic tract (STT) neurons to the pain and neurogenic hyperalgesia produced by an intradermal injection 100 micrograms capsaicin was investigated. Electrophysiological responses identified STT recorded anesthetized monkeys were compared with psychophysical measurements obtained humans using identical stimuli. 2. Magnitude estimates after or vehicle. Capsaicin immediate burning that most intense within 15 s then declined over next 10-30 min. vehicle...

Psychophysical measurements of pain and mechanical hyperalgesia were obtained following different doses capsaicin injected intradermally into the forearms human subjects. Each subject received a 10 μ1 injection vehicle 0.01, 0.1, 1, 100μg. The relationship between dose magnitude duration was determined using method estimation. In addition to pain, produced flare hyperalgesia. area time course measured as function capsaicin. based on averaged responses all subjects, increased negatively...

In vivo somatosensory stimuli evoked the release of substance P from primary afferent neurons that terminate in spinal cord and stimulated endocytosis receptors rat neurons. The distal dendrites showed receptor internalization underwent morphological reorganization, changing a tubular structure to one characterized by swollen varicosities connected thin segments. This dendritic structural reorganization provided specific image activated P. Thus can drive reversible changes central nervous...

Capsaicin applied topically to human skin produces itching, pricking and burning sensations due excitation of nociceptors. With repeated application, these positive sensory responses are followed by a prolonged period hypalgesia that is usually referred as desensitization, or nociceptor inactivation. Consequently, capsaicin has been recommended treatment for variety painful syndromes. The precise mechanisms account desensitization unclear. present study was performed determine if...

1. A local cutaneous injury can produce primary hyperalgesia within the injured area and secondary in normal surrounding skin. An intradermal injection of capsaicin humans causes intense pain to heat mechanical stimuli Psychophysical studies supported conclusions that was predominantly type depended on one set neurons sensitizing another (“neurogenic hyperalgesia”) latter is located central not peripheral nervous system. To further test this hypothesis search for neural mechanisms...

Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these resulted in a reduction thermal hyperalgesia and mechanical allodynia associated persistent neuropathic inflammatory pain states. This loss appeared to be permanent. Responses mildly painful stimuli morphine analgesia unaffected by this treatment. These results identify target for treating suggest that small population SPR-expressing dorsal horn cord plays pivotal...

The ability of capsaicin to excite and subsequently desensitize a select group small sensory neurons has made it useful tool study their function. For this reason, application the skin been used for variety painful syndromes. We examined whether intradermal injection produced morphological changes in cutaneous nerve fibers that would account its analgesic properties by comparing innervation capsaicin-treated with psychophysical measures sensation. At various times after injection, were...

Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by increased spontaneous activity, enlarged receptive field (RF) areas, an increase in responses evoked large small caliber primary afferent fibers. Sensitization often occurs following tissue injury inflammation believed contribute hyperalgesia. Windup the progressive magnitude C-fiber produced repetitive activation C-fibers. In present study, we tested hypothesis that windup leads central...

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch blocked using antihistamines, others cannot these constitute important clinical problem. Little information available on the mechanisms underlying that produced by nonhistaminergic mechanisms. We examined responses spinothalamic tract neurons to histaminergic and, for first time, stimuli. Fifty-seven primate (STT) were identified antidromic activation...

In previous studies, we have shown that loss of spinal neurons possess the substance P receptor (SPR) attenuated pain and hyperalgesia produced by capsaicin, inflammation, nerve injury. To determine role SPR-expressing in modulating hyperalgesia, responses superficial deep lumbar dorsal horn evoked mechanical heat stimuli capsaicin were made after ablation using selective cytotoxin conjugate P-saporin (SP-SAP). Morphological analysis electrophysiological recordings intrathecal infusion...

The increasing use of transgenic mice for the study pain mechanisms necessitates comprehensive understanding murine somatosensory system. Using an in vivo mouse preparation, we studied response properties tibial nerve afferent fibers innervating glabrous skin. Recordings were obtained from 225 identified by mechanical stimulation Of these, 106 classed as Aβ mechanoreceptors, 51 Aδ fibers, and 68 C fibers. mechanoreceptors had a mean conduction velocity 22.2 ± 0.7 (SE) m/s (13.8–40.0 m/s)...

Withdrawal responses to heat and mechanical stimuli applied the plantar surface of rat hindpaw were measured before after an intraplantar injection capsaicin. In separate groups rats, capsaicin doses 1, 10 30 μg, vehicle given into center in a volume μl. latency evoked by radiant frequency withdrawal (von Frey monofilaments) obtained from both hindpaws injection. Hyperalgesia was defined as decrease hyperalgesia indicated increase response frequency. Intraplantar nocifensive behavior...

Psychophysical measurements of itch and itchy skin ("alloknesis"--itch produced by innocuous mechanical stimulation) were obtained in human volunteers following intracutaneous or subcutaneous injections histamine papain into the volar forearm. Histamine given doses 0.1, 1, 10 micrograms microliters saline. The effects depth injection temperature on latency, magnitude, duration examined. Also, dose-response functions for area alloknesis histamine. Finally, neural mechanisms underlying spread...

Responses of cutaneous nociceptors to natural stimuli, particularly mechanical and heat have been well documented. Although are excited by noxious cold there few studies their stimulus-response functions for stimuli over a wide range stimulus temperatures. Furthermore, the proportion is not clear. In present study, we examined responses mechanosensitive A delta-nociceptors low-threshold mechanoreceptors that included temperatures <0 degrees C. Electrophysiological recordings were made from...

Itch of peripheral origin requires information transfer from the spinal cord to brain for perception. Here, primate spinothalamic tract (STT) neurons lumbar were functionally characterized by in vivo electrophysiology determine role these cells transmission pruriceptive information. One hundred eleven STT identified antidromic stimulation and then recorded while histamine cowhage (a nonhistaminergic pruritogen) sequentially applied cutaneous receptive field each cell. Twenty percent...

Painful peripheral neuropathy is a dose-limiting complication of chemotherapy. Cisplatin produces cumulative toxic effect on nerves, and 30–40% cancer patients receiving this agent experience pain. By modeling cisplatin-induced hyperalgesia in mice with daily injections cisplatin (1 mg/kg, i.p.) for 7 d, we investigated the anti-hyperalgesic effects anandamide (AEA) cyclohexylcarbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597), an inhibitor AEA hydrolysis. Cisplatin-induced mechanical...

Chronic pain is a major characteristic feature of sickle cell disease (SCD). The refractory nature and the development chronic syndromes in many patients with SCD suggest that central neural mechanisms contribute to this disease. We used HbSS-BERK mice, which show features similar those observed SCD, determined whether sensitization nociceptive neurons spinal cord contributes hyperalgesia SCD. Electrophysiological recordings action potential activity were obtained from single identified...