Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eyeassociated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain.

Patients undergoing breast surgery for cancer may develop chronic pain. We evaluated the effect of mexiletine and gabapentin on the acute and chronic pain after breast surgery for cancer. Both drugs reduced the postoperative analgesic requirements, and particularly, gabapentin reduced pain after movement. The overall incidence of chronic pain was unaffected except for burning pain.

BackgroundATP-sensitive potassium (KATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of KATP channels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both KATP channels and participate in the pathophysiology and pharmacology of neuropathic pain. Therefore, we investigated NO modulation of KATP channels in control and axotomized DRG neurons.ResultsCell-attached and cell-free recordings of KATP currents in large DRG neurons from control rats (sham surgery, SS) revealed activation of KATP channels by NO exogenously released by the NO donor SNAP, through decreased sensitivity to [ATP]i.This NO-induced KATP channel activation was not altered in ganglia from animals that demonstrated sustained hyperalgesia-type response to nociceptive stimulation following spinal nerve ligation. However, baseline opening of KATP channels and their activation induced by metabolic inhibition was suppressed by axotomy. Failure to block the NO-mediated amplification of KATP currents with specific inhibitors of sGC and PKG indicated that the classical sGC/cGMP/PKG signaling pathway was not involved in the activation by SNAP. NO-induced activation of KATP channels remained intact in cell-free patches, was reversed by DTT, a thiol-reducing agent, and prevented by NEM, a thiol-alkylating agent. Other findings indicated that the mechanisms by which NO activates KATP channels involve direct S-nitrosylation of cysteine residues in the SUR1 subunit. Specifically, current through recombinant wild-type SUR1/Kir6.2 channels expressed in COS7 cells was activated by NO, but channels formed only from truncated isoform Kir6.2 subunits without SUR1 subunits were insensitive to NO. Further, mutagenesis of SUR1 indicated that NO-induced KATP channel activation involves interaction of NO with residues in the NBD1 of the SUR1 subunit.ConclusionNO activates KATP channels in large DRG neurons via direct S-nitrosylation of cysteine residues in the SUR1 subunit. The capacity of NO to activate KATP channels via this mechanism remains intact even after spinal nerve ligation, thus providing opportunities for selective pharmacological enhancement of KATP current even after decrease of this current by painful-like nerve injury.

We evaluated the effect of multimodal analgesia on acute and chronic pain after breast surgery for cancer. Fifty patients scheduled for breast cancer surgery were blindly randomized to receive gabapentin, eutectic mixture of local anesthetics cream, and ropivacaine in the wound or three placebos. Pain (visual analog scale) and analgesics were recorded in the postanesthesia care unit (PACU) 3, 6, and 9 h and 8 days after surgery. Three and 6 mo later, patients were assessed for chronic pain. The treatment group consumed less paracetamol in the PACU (469 versus 991 mg; P < 0.002) and less Lonalgal (1.0 versus 4.4 tablets; P = 0.003) than the controls, exhibited lower visual analog scale scores at rest in the PACU (P = 0.001) and on postoperative Days 1, 3, and 5 (P = 0.040, P = 0.015, and P = 0.045, respectively), and after movement in the PACU (P = 0.001) and on postoperative Days 2, 4, and 8 (P = 0.028, P = 0.007, and P = 0.032, respectively). Three and 6 mo after surgery, 18 of 22 (82%) and 12 of 21 (57%) of the controls reported chronic pain versus 10 of 22 (45%) and 6 of 20 (30%) in the treatment group (P = 0.028 and P = 0.424, respectively); 5 of 22 and 4 of 21 of the controls required analgesics versus 0 of 22 and 0 of 20 of those treated (P = 0.048 and P = 0.107, respectively). Multimodal analgesia reduced acute and chronic pain after breast surgery for cancer.

Dry eye symptoms more closely align to non-ocular pain, depression and PTSD than to tear film parameters.