To elucidate the effect of chronic inflammation on spinal nociceptive neurons in the elderly, we compared nocifensive behavior, peripheral inflammatory responses, and spinal dorsal horn neuronal activities between the aged (29-34 mo) and adult (7-12 mo) male rats after injection of complete Freund's adjuvant (CFA) into the hind paw. Aged rats exhibited a significantly lower mechanical paw withdrawal threshold before inflammation. However, after CFA injection mechanical allodynia developed in both adult and aged rats after CFA injection. The changes of foot temperature and thickness after CFA injection were greater and lasted longer in aged than in adult rats. Sets of 124 wide dynamic range (WDR) neurons (aged: 59, adult: 65) and 26 nociceptive specific (NS) neurons (aged: 13, adult: 13) were recorded from the lumber spinal dorsal horn. NS neurons from the inflamed adult rats showed significantly higher responses to noxious mechanical stimulation than those in aged rats, whereas WDR neurons from inflamed adult and aged rats were similar. Background activity of WDR neurons from the adult rats increased after CFA, whereas WDR neurons of aged rats and NS neurons from either group were not. The afterdischarge followed by noxious mechanical stimulation was significantly greater for WDR neurons in both adult and aged rats, whereas no significant differences were observed in NS neurons. Two days after CFA injection, Fos expression increased similarly in aged and adult rats. Thus the aged rats showed enhanced peripheral inflammatory responses to CFA injection with only a slight change in dorsal horn neuronal activity. Together with our previous finding that nociceptive neurons in aged rats exhibit hyperexcitability, these results suggest that the dorsal horn nociceptive system becomes sensitized with advancing age and its excitability cannot be further increased by inflammation.

Recordings were made from single thalamic units in the urethan-chloralose anesthetized cat. Altogether 2,905 trigeminal single units having a receptive field in the contralateral trigeminal integument were isolated from the somatosensory part of nucleus ventralis posteromedialis, or VPM proper. Each isolated unit was tested for responses to a series of mechanical stimuli. The stimuli included brushing the skin, touch, pressure, noxious pinch, and pinpricks. The majority of VPM proper units responded with the greatest discharge frequency to gentle mechanical stimulation: either hair movement or light pressure to the trigeminal integument, but 341 units were identified as trigeminal nociceptive units. They were partitioned into two functionally defined subclasses, nociceptive specific (NS) and wide dynamic range (WDR) units, but not intermingled with low-threshold mechanoreceptive (LTM) units. Both NS and WDR units were found at or near the margin of the VPM proper but not outside this nucleus. This marginal area was referred to as the shell region of the VPM proper. A total of 248 NS units was found within the shell region of the caudal third of the VPM proper. This part was called the NS zone. These units were somatotopically organized. In the rostral part of the NS zone, ophthalmic NS units having a receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary NS units occurred dorsomedially, and mandibular NS units were found ventromedially. In the caudal part of the NS zone, maxillary NS units were encountered in the dorsal shell region, whereas mandibular NS units were found in the ventromedial shell region. Ophthalmic NS units were not found in this part of the NS zone. Altogether 93 WDR units were encountered in the shell region of the VPM proper. They were confined to a narrow band approximately 300 micron wide just rostral to the NS zone. These units were somatotopically organized. Ophthalmic WDR units having a low-threshold center of the receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary WDR units were located dorsomedially, and mandibular WDR units were located ventromedially. The majority of maxillary as well as mandibular WDR units were activated by electrical stimulation of the contralateral maxillary and/or mandibular canine tooth pulp afferents. Both NS and WDR zones of the VPM proper extended into the shell region of the nucleus ventralis posterolateralis (VPL).(ABSTRACT TRUNCATED AT 400 WORDS)

The aim of the present study was to investigate whether melittin, the principal toxin of the honeybee (Apis mellifera) venom, can be used as an algogenic agent in the study of pain in humans. Five micrograms of melittin in 0.5 ml of saline was intradermally injected into the volar aspect of the forearm. Resultant pain was scored by a visual analogue scale (VAS), and skin temperature change was analyzed by means of a computer-assisted infrared thermography. Intradermal melittin temporarily produced severe pain, followed by a sustained increase in skin temperature. The skin temperature increase peaked in about 10 min and outlasted 1 h. Topical application of 10% lidocaine gel did not significantly suppress the melittin-induced pain, but markedly suppressed both the increase in the peak temperature and the area of temperature increase. In conclusion, 5 microg of melittin is sufficient to produce pain in humans and 10% lidocaine gel differentially decreases the melittin-induced axon reflex without any significant analgesic effect.

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