Pain
-
Tactile allodynia and thermal hyperalgesia, two robust signs of neuropathic pain associated with experimental nerve injury, have been hypothesized to be mechanistically distinguished based on (a) fiber types which may be involved in the afferent input, (b) participation of spinal and supraspinal circuitry in these responses, and (c) sensitivity of these endpoints to pharmacological agents. Here, the possibility that nerve-injury induced tactile allodynia and thermal hyperalgesia may be mediated via different afferent fiber input was tested by evaluating these responses in sham-operated or nerve-injured (L5/L6) rats before or after a single systemic injection of resiniferatoxin (RTX), an ultrapotent analogue of the C-fiber specific neurotoxin, capsaicin. Tactile allodynia, and three measures of thermal nociception, tail-flick, paw-flick and hot-plate responses, were determined before and at various intervals for at least 40 days after RTX injection. ⋯ The hypothesis that tactile allodynia may be due to inputs from large (i.e. A beta) afferents offers a mechanistic basis for the observed insensitivity of this endpoint to intrathecal morphine in this nerve-injury model. Further, these data suggest that clinical treatment of neuropathic pains with C-fiber specific agents such as capsaicin are unlikely to offer significant therapeutic benefit against mechanical allodynia.
-
The mechanisms underlying the relief of neuropathic pain of peripheral origin by spinal cord stimulation (SCS) are poorly understood. The present study was designed to investigate the effects of SCS on evoked and spontaneous discharges in dorsal horn neurons in intact and in nerve-injured rats subjected to partial sciatic nerve ligation according to Seltzer et al. (1990). Tactile sensitivity in the hind paw was assessed in behavioral tests using von Frey filaments. ⋯ In non-allodynic and control rats, SCS had no significant depressive effects on the evoked responses and spontaneous discharge. The results suggest that SCS may provide a suppressive action on dorsal horn neuronal hyperexcitability associated with signs of peripheral neuropathy. The suppressive effect of SCS on tactile allodynia, as previously observed in behavioral experiments, presumably corresponds to a normalization of the excitability of WDR cells in response to innocuous stimuli.
-
Previous work demonstrated that, in rats, intrathecal GR89696, a putative kappa-2 opioid receptor agonist, inhibited hyperalgesia to noxious heat in an inflamed hind paw (anti-hyperalgesic effect). Non-inflamed paws were not influenced by kappa-2 receptor activation. The question addressed in this study was whether GR89696 was as effective in blocking hyperalgesia and allodynia in nerve injury models as it was in the inflammation model. ⋯ Naloxone (1 mg/kg, i.p.) reversed the anti-hyperalgesic and anti-allodynic effects of GR89696. The mu agonist DAMGO (6 nmoles, i.t.) and the kappa-1 agonist U69593 (100 nmoles, i.t.) only partially reversed hyperalgesia and allodynia. These findings suggest that kappa-2 opioid receptors may be a useful target for the pharmacological control of hyperalgesia and allodynia.
-
Randomized Controlled Trial Multicenter Study Clinical Trial
Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study.
Oral transmucosal fentanyl citrate (OTFC) is a novel opioid formulation in which the potent synthetic mu-agonist fentanyl is embedded in a sweetened matrix that is dissolved in the mouth. It is undergoing investigation as a treatment for cancer-related breakthrough pain, a prevalent phenomenon defined as a transitory flare of moderate to severe pain that interrupts otherwise controlled persistent pain. There have been no controlled trials of other treatments for this condition. ⋯ OTFC appears to be a safe and effective therapy for breakthrough pain, and dose titration can usually identify a unit dose capable of providing adequate analgesia. If the lack of a relationship between the effective OTFC dose and fixed schedule opioid regimen is confirmed, dose titration may be needed in the clinical use of this formulation. Further investigation of OTFC as a specific treatment for breakthrough pain is warranted.
-
Randomized Controlled Trial Clinical Trial
Spatial and temporal summation of sensory and affective dimensions of deep somatic pain.
There is considerable evidence in support of differential information processing of the sensory-discriminative and motivational-affective meanings of pain. The purpose of this work was to examine whether temporal (acute, tonic, persistent) and spatial (local, regional, widespread) aspects of deep somatic pain influence the sensory and affective dimensions of pain. Acute pain consisted of a short bout of pain, lasting about 100 s. ⋯ Affective scores showed the most significant increases from acute to tonic pain, particularly with greater spatial involvement. The significant increases in sensory scores observed when contrasting persistent facial pain alone and in combination with widespread musculoskeletal pain was attributed to the broader body experience. Because the perceptual correlates of tonic and matched persistent (chronic) pain states were similar, we concluded that it does not require months for the development of the sensory and affective meaning of persistent pain as assumed.